Quercetin Impact nyob rau hauv Pancreatic Cancer: Ib qho kev piav qhia ntawm nws cov teebmeem kev kho mob

Yog xav paub ntxiv hu rau emailtina.xiang@wecistanche.com
Mob qog noj ntshav pancreatic(PC) yog kab mob qog noj ntshav uas tuag taus, thiab nws cov neeg tuag tau nce thoob ntiaj teb. Kev kuaj mob qog noj ntshav no nyuaj, vim nws tsis tshua muaj cov tsos mob tshwm sim, thiab cov neeg mob feem ntau nthuav tawm cov qog uas tsis tuaj yeem kho tau muaj 5- xyoo muaj sia nyob tom qab kuaj mob. Hais txog kev kho mob, ntau qhov kev txhawj xeeb kuj tau tshwm sim, vim tias feem ntau cov qog pom muaj nyob rau theem siab heev. Tam sim no, cov tshuaj tiv thaiv kab mob-nplua nuj cov khoom noj tau siv los tswj PC. Ntawm cov bioactive molecules, flavonoid tebchaw tau qhia zoo heev anticancer peev xwm, xws liquercetin, uas tau siv los ua ib qho tshuaj ntxiv lossis lwm yam tshuaj rau PC kev kho mob los ntawm inhibitory lossis stimulatory biological mechanisms suav nrog autophagy, apoptosis, cell loj hlob txo lossis inhibition, EMT, oxidative stress, thiab txhim kho rhiab heev rau cov tshuaj tua kab mob. Kev lees paub tias cov khoom lag luam ntuj no muaj txiaj ntsig zoo rau kev kho mob qog noj ntshav tau txhawb cov kws tshawb fawb kev txaus siab rau kev tshawb fawb ntau dua los siv tshuaj ntsuab rau kev tiv thaiv kab mob. Tsis tas li ntawd, vim tus nqi kim thiab tus nqi siab ntawm cov tshuaj tiv thaiv kab mob, tau sim siv quercetin tab sis kuj muaj lwm yam.flavonoidstiv thaiv thiab kho PC. Raws li kev tshawb fawb ntsig txog, nws tau pom tias covquercetincompound muaj qhov cuam tshuam loj rau cov kab mob qog noj ntshav nrog rau cov qauv tsiaj. Yog li ntawd, nws tuaj yeem siv los ua cov tshuaj ntxiv los kho ntau yam qog noj ntshav, tshwj xeebmob qog noj ntshav pancreatic. Qhov kev tshuaj xyuas no yog tsom rau kev sib tham txog cov teebmeem kev kho mob ntawmquercetinlos ntawm kev tsom mus rau txoj kev taw qhia molecular thiab txheeb xyuas kev tiv thaiv kev loj hlob, cell proliferation, antioxidative stress, EMT, induction ntawm apoptotic, thiab autophagic nta.

1. Taw qhia

Mob qog noj ntshav pancreatic(PC) yog ib qho mob qog noj ntshav ntau zuj zus ntawm txoj hnyuv (GIT), nrog cov ciaj sia taus tsawg dua 5 feem pua ​​​​ntawm 5 xyoos tom qab kuaj mob, thiab kwv yees li 50 feem pua ​​​​ntawm tag nrho cov neeg mob tuag dhau 6 lub hlis ntawm kev kuaj mob. Raws li kev kwv yees hauv Tebchaws Meskas, PC yuav dhau los ua qhov thib ob feem ntau ua rau mob qog noj ntshav hauv nees nkaum rau peb caug xyoo tom ntej. Txawm li cas los xij, cov neeg mob 'kev kwv yees nrog cov qog nqaij hlav hauv cheeb tsam thiab kev hwm tseem tsis zoo nrog tsuas yog 20 feem pua ​​​​ntawm cov ciaj sia taus tom qab phais [1]. Tsis tas li ntawd, nyob rau hauv txoj kab nrog GLOBOCAN 2018 kev soj ntsuam, PC uas suav txog kwv yees li 459,000 tus neeg mob tshiab thiab 432,{10}} kev tuag yog thib xya ua rau mob qog noj ntshav thoob ntiaj teb [2]. Hauv Tebchaws Europe, nws tau xav tias PC yuav nrawm dua li mob qog noj ntshav ntawm lub mis raws li qhov thib peb ua rau mob qog noj ntshav tom qab mob qog noj ntshav thiab mob ntsws [3].

PC yog tus yam ntxwv raws li cov qog ntawm exocrine pancreas thiab ductal adenocarcinoma; Txawm li cas los xij, ib qho me me ntawm cov neeg mob kuj sawv cev rau cov qog neuroendocrine. Tseeb tiag, pancreatic intraepithelial neoplasia los yog cov kab mob ua ntej yog qhov ua haujlwm ntawm qhov tau txais cov kev hloov pauv caj ces uas ua rau pom pom tus kab mob pancreatic ductal adenocarcinoma (PDA) [4]. Hmoov tsis zoo, PC cov tsos mob tsis pib mus txog rau theem siab ntawm mob qog noj ntshav thiab feem ntau tsis meej, nrog rau xeev siab, ntuav, mob plab hnyav, thiab poob phaus. Tsis tas li ntawd, cov kev tshawb fawb yav dhau los tau qhia tias hom 2 mob ntshav qab zib mellitus, tsev neeg keeb kwm, rog rog, thiab kev haus luam yeeb yog qhov tseem ceeb rau PC [1–5]. Yog li ntawd, cov kev tshawb fawb tau coj mus rau kev tiv thaiv PC. Ntau yam ntawm cov kev tshawb fawb tsis ntev los no tau tshawb txog cov yam ntxwv ntawm cov tshuaj phytochemicals thiab tau qhia tias polyphenols,flavonoids, thiab flavones tuaj yeem tiv thaiv ntau hom qog nqaij hlav [6]. Flavonoids yog cov metabolites theem nrab ntawm cov nroj tsuag nrog kev ua haujlwm tshuaj (Table 1). Yog li ntawd, txiv hmab txiv ntoo los yog zaub, xws li cocoa thiab kas fes, yog qhov tseem ceeb ntawmflavonoids[7, 8] ib. Raws li cov qauv tshuaj, oxidation degree, thiab unsaturation ntawm kev sib txuas cov saw, flavonoids yog categorized rau 6 lub ntsiab chav kawm: isoflavonoids, flavones, flavanols, flavanones, flavonols, thiab anthocyanidins [9].Quercetinthiab kaempferol yog qee qhov feem ntau pom flavonols [10]. Quercetin (C15H10O7) yog hu los ntawm IUPAC (International Union of Pure and Applied Chemistry) raws li nram no: 3,3,4,5,7- pentahydroxyflavone thiab 2-(3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-ib [11]. Nws tau raug sau tseg tiasquercetinmuaj tshuaj tua kab mob, tshuaj tua kab mob antioxidant, cytotoxic, hepatoprotective, thiab tshuaj tiv thaiv kab mob [12]. Tshwj xeeb, ob qho tib si quercetin thiab nws cov derivatives tuaj yeem tiv thaiv cov kab mob qog noj ntshav los ntawm kev tswj cov kab mob ntawm tes. Txawm li cas los xij, cov tshuaj tiv thaiv kab mob thiab tshuaj tua kab mob ntawm quercetin yog lub hauv paus tseem ceeb rau nws cov kev ua haujlwm raws li lub voj voog ntawm tes inhibitors, thiab cov nyhuv apoptosis-inducing ntawm quercetin muaj lub luag haujlwm tseem ceeb hauv tshuaj tiv thaiv kab mob [13, 14]. Qhov tseem ceeb, quercetin yog ib qho phytochemical hauv kev noj zaub mov tsis tu ncua ntawm tib neeg thoob ntiaj teb vim nws tuaj yeem pom dav hauv cov khoom noj txhua hnub, xws li tshuaj yej, kas fes, zaub sib txawv, txiv ntseej, thiab txiv hmab txiv ntoo [15]. Quercetin thiab nws cov derivatives ua rau muaj kev cuam tshuam lom rau kev loj hlob ntawm cov qog nqaij hlav hlwb; Yog li ntawd, cov txheej txheem metabolic ntawm quercetin tau suav tias yog qhov tseem ceeb hauv cov nroj tsuag kev hloov pauv. Ntau qhov kev tshawb fawb tsis ntev los no tau tsom mus rau cov ntsiab lus quercetin ntawm cov txiv hmab txiv ntoo thiab zaub rau nws cov hom phiaj kho mob [16–19]. Tsis tas li ntawd, raws li tau hais los ntawm Harwood thiab al. [20], coj mus muag siv tauquercetintuaj yeem noj ntawm qhov ncauj ntawm koob tshuaj 1 g txhua hnub, uas yog nqus tau txog 60 feem pua ​​thiab muaj kev nyab xeeb txaus. Hauv qhov kev nkag siab no, qhov kev tshuaj xyuas no yog los tham txog cov khoom tiv thaiv kabmob kheesxaws ntawm quercetin tawm tsam PC, xav txog nws tus nqi qis hauv kev sib piv rau cov tshuaj hluavtaws. Tsis tas li ntawd, qhov tseeb tiam sis ntawm quercetin nta thiab lawv cov txheej txheem molecular hauv kev kho mob qog noj ntshav kuj tau sau tseg. Yog li, cov kev tshawb fawb sib txawv tau txheeb xyuas cov txheej txheem uas yuav tshwm sim los ntawm qhov uas quercetin exerts nws cov teebmeem antitumor tiv thaiv.mob qog noj ntshav pancreatichlwb. Txij li thaum tsis muaj ib tsab xov xwm tshuaj xyuas ntawm cov ncauj lus no raws li peb cov kev tshawb fawb, peb tsom los tham txog cov txiaj ntsig kho mob ntawm quercetin tiv thaiv.mob qog noj ntshav pancreatichlwb thawj zaug.

2. Pancreatic Cancer(PC)

Tam sim no, nrog rau qhov nruab nrab {{0}} xyoo muaj sia nyob tus nqi, PC tau kwv yees tias yog qhov thib ob ua rau mob qog noj ntshav los ntawm 2030 hauv Tebchaws Meskas [21–23]. Qhov ua tau ntawm kev tsim PC yog kwv yees li 1.5 feem pua ​​​​hauv ob leeg poj niam txiv neej [23], txawm hais tias feem ntau tshwm sim hauv cov neeg laus, ntawm 70 thiab 80 xyoo, feem ntau nyob rau hauv cov ntaub ntawv tsis muaj chaw thiab kho tsis tau [21, 24]. PC feem ntau nyob twj ywm undetectable mus txog rau thaum nws hloov mus rau hauv ib tug metastatic qog [25]. Thaum lub etiology ntawm PC tsis tau to taub tag nrho, ntau yam kev pheej hmoo ntawm caj ces thiab ib puag ncig tau paub tias yuav ua rau muaj kev pheej hmoo, suav nrog kev haus luam yeeb, rog rog, noj zaub mov muaj roj tsiaj, cystic fibrosis, thiab caj ces predispositions [26]. Raws li Huang et al. [27], qhov tshwm sim ntau tshaj plaws thiab kev tuag ntawm PC yog nyob rau hauv cov teb chaws uas muaj kev loj hlob ntawm tib neeg siab heev los yog cov hnub nyoog-tus qauv (ASRs) los yog cov teb chaws uas muaj ntau dua ntawm kev haus cawv, haus luam yeeb, kub siab, lub cev tsis muaj zog, rog, thiab siab. cov roj cholesterol. Qhov feem ntau tshwm sim ntawm PC tau tshaj tawm nyob rau hauv Western Europe (ASR, 8.3), North America (ASR, 7.6), thiab Central thiab Eastern Europe (ASR, 7.5). Qhov tshwm sim ntawm PC muaj txiv neej rau poj niam piv ntawm 1.4: 1.0. Cov ncauj lus kom ntxaws ntxiv txog PC tshwm sim thiab kev tuag raws li thaj av thiab poj niam txiv neej tau nthuav tawm hauv cov ntaub ntawv tseem ceeb [27].

Kev kuaj mob ua ntej yuav pab tau zoo heev hauv kev kho mob zoo ntawm qhov mob no, txawm tias tsis tshua muaj tshwm sim ntawm cov neeg mob. Hais txog kev kho mob, kev phais, kws khomob, thiab kev siv xov tooj cua yog cov tswv yim kho mob feem ntau siv rau kev kho PC. Qhov tseeb, cov txheej txheem ntawm kev kho mob yog kev phais tom qab kho adjuvant; Txawm li cas los xij, qhov rov tshwm sim ntawm 70-80 feem pua ​​​​ntawm cov qog resected thaum kawg tshwm sim. Cov neeg mob uas tsim nyog rau kev phais kev phais tsuas yog yuav luag 10-15 feem pua ​​​​ntawm tag nrho cov neeg mob uas muaj PC siab heev. Nrog rau feem ntau ntawm cov neeg mob tau kuaj pom nyob rau theem tom ntej, chemotherapy tseem yog qhov kev kho mob nkaus xwb rau PC. 5-Fluorouracil (5-FU) thiab gemcitabine (GMC), ib leeg lossis ua ke nrog hluav taws xob, yog cov txheej txheem tshuaj khomob rau PC txoj kev kho mob, txawm tias feem ntau cov lus teb feem ntau qis dua 31 feem pua. GMC muaj qee qhov zoo dua 5-FU, xws li lub peev xwm los txo cov tsos mob ntawm tus kab mob feem ntau thiab muaj qhov ua kom muaj sia nyob tsawg; Txawm li cas los xij, nws tsis tuaj yeem txuas ntxiv qhov nruab nrab muaj sia nyob ntau tshaj li 6 lub hlis, zoo li lwm cov kws khomob [28, 29]. Yog li ntawd, nrog rau kev ua tiav tsis tiav ntawm cov qauv kev kho tam sim no, kev tshawb nrhiav cov tswv yim kho tshiab thiab ua tau zoo thiab cov neeg sawv cev yog qhov xav tau sai.

3. Ib txwm tshwm sim Phytochemicals rau Anticancer Lub Hom Phiaj

Ntau yam kev soj ntsuam thiab cov kev tshawb fawb yav tom ntej tau qhia txog kev sib koom tsis ncaj ntawm cov txiv hmab txiv ntoo thiab zaub noj nrog qhov tshwm sim ntawm qee cov qog nqaij hlav thiab lub peev xwm loj ntawm cov khoom sib txuas los hloov lub ntuj nws tory ntawm carcinogenesis [30–32]. Nroj tsuag nrog qee cov tshuaj bioactive uas tsis yog cov khoom sib xyaw ua ke cais, tus yam ntxwv thiab pom tias yog phytochemicals tau tshawb nrhiav ntau dua rau lawv lub peev xwm los kho cov kab mob sib txawv, tshwj xeeb tshaj yog mob qog noj ntshav [33–41]. Nws zoo nkaus li tias cov khoom ntuj tseem tuav cov kev xaiv zoo tshaj plaws los nrhiav cov khoom tshiab zoo hauv kev kho tib neeg cov kab mob [42]. Tsis tas li ntawd, kev txhim kho ntawm kev tshawb fawb thev naus laus zis xws li genome mining, genetic engineering, thiab siv cov nanoparticles ua cov cab kuj [43] txhim kho kev tshawb pom cov tshuaj tshiab hauv kev kho mob qog noj ntshav [44]. Lo lus 'phytochemical' yog hais txog cov nroj tsuag (phyto hauv Greek) tshuaj. Ntau yam ntawm cov phytochemicals no tuaj yeem tswj hwm ntau yam ntawm cov xov tooj ntawm tes taw qhia txoj hauv kev uas koom nrog oxidative kev nyuaj siab, kev loj hlob, kev loj hlob, kev sib txawv, thiab kev tuag [37, 45–48]. Piv txwv li, lawv nthuav tawm cov khoom antioxidant los ntawm kev cuam tshuam rau Nrf2-Keap1 txoj hauv kev, thaum ua kom, Nrf2 hloov mus rau hauv lub nucleus, khi rau ARE (antioxidant teb cov ntsiab lus) lossis EpREs (electrophile teb cov ntsiab lus), thiab ua kom cov lus qhia ntawm ATP. Nyob ntawm cov tshuaj efflux twj tso kua mis, detoxification enzymes, thiab endogenous antioxidants [49]. Cov xwm txheej no thaum kawg ua rau muaj kev tiv thaiv cov hlwb tiv thaiv ROS (reactive oxygen hom) [50, 51]. Phytochemicals tseem tuaj yeem cuam tshuam cov qog nqaij hlav thiab ua rau apoptosis hauv cov hlwb ua ntej neoplastic lossis neo-plastic hlwb los ntawm kev cuam tshuam rau lub voj voog ntawm tes, JAK-STAT, NF-κB, thiab cytochrome C signaling pathways [52, 53]. Ib qho ntawm cov tshuaj phytochemicals yog garcinol, polyisoprenylated Benzophenone uas tuaj yeem cuam tshuam STAT-3 txoj hauv kev los ntawm kev tawm tsam cov kinases (c-Src, JAK1, thiab JAK2) hauv HNSCC hlwb. Garcinol tseem inhibits NF-κB ua kom los ntawm kev tawm tsam ntawm TGF- thiab inhibitor ntawm IκB kinase (IKK) ua kom hauv HNSCC hlwb [54]. Tsis tas li ntawd, Li et al. qhia tias garcinol tiv thaiv kev loj hlob ntawm tib neeg HNSCC xenograft qog nyob rau hauv txiv neej athymic nu/nu nas [54]. Nws tuaj yeem xaus lus tias garcinol muaj peev xwm tiv thaiv qog nqaij hlav hauv lub taub hau thiab caj dab los ntawm kev tawm tsam ntawm ntau yam proinflammatory cascades. Activator protein 1 (AP-1) yog qhov tseem ceeb ntawm kev hloov pauv hauv kev tswj hwm ntawm ntau cov txheej txheem ntawm tes muaj feem cuam tshuam rau cov kab mob inflammatory thiab mob qog noj ntshav. Muaj ntau yam ntuj tsim xws li kaempferide, resveratrol, apigenin, isorhamnetin, citrifolinoside A, viscolin, curcumin, thiabquercetintuaj yeem hloov kho AP-1-txoj kev taw qhia txoj hauv kev rau kev tiv thaiv qog noj ntshav thiab kev cuam tshuam [55].

Ntawm cov plethora ntawm biologically active phytochemicals nrog anticancer muaj peev xwm, lawv yog tshuaj categorized rau phenolics, carotenoids, phytosterols, organosulfur tebchaw, thiab nitrogen-muaj compounds [56, 57]. Phenolics yog structurally characterized nrog ib tug (phenolic acids) los yog ntau tshaj (polyphenols) aromatic rings nrog ib los yog ntau tshaj hydroxyl (OH) pawg [58]. Phenolic compounds tuaj yeem muab faib ua flavonoids thiab nonflavonoids [59]. Flavonoids, suav nrog glycosides, aglycone, thiab methylated derivatives, muaj ib nrab ntawm cov phenolic tebchaw [60]; flavonoids tau muab faib ua flavones, flavanones, flavanonols, flavanols, flavononls, isoflavones, chalcones, thiab anthocyanidins [61, 62]. Nonflavonoids kuj muaj ntau pawg uas suav nrog stilbenes, phenolic acids, lignans, coumarins, thiab tannins [63] (Daim duab 1).

4. Flavonoids thiab Anticancer Effects: Qhov tseem ceeb ntawm Quercetin

Nyob rau hauv chav kawm ntawm polyphenolic flavonoid tebchaw thiab subclass ntawm flavonols, quercetin yog ubiquitous nyob rau hauv cov khoom noj txhua hnub, nrog rau ntau yam nroj tsuag, zaub, txiv ntseej, noob, txiv hmab txiv ntoo, tshuaj yej, thiab liab cawu cub [64, 65]. Txawm li cas los xij, cov txiv hmab txiv ntoo thiab cov nroj tsuag tau raug kawm raws li kev cog lus ntawm quercetin [17, 66–68]. Querce tin muaj cov yam ntxwv ntawm flavonoids (caj qaum C6-C3-C6) nyob rau hauv uas ob lub nplhaib benzene tau sib koom los ntawm 3-carbon heterocyclic pyrone [69, 7{{3{{ 31}}}}]. Quercetin muaj ob lub tshuaj tua kab mob antioxidant hauv cov qauv no, uas tso cai rau nws los ua tus neeg sawv cev dawb radical scavenging thiab koom nrog cov hlau hloov pauv hloov pauv [69]. Qhov kev npaj zoo tshaj plaws ntawm catechol thiab OH pawg ntawm C3, txoj hauj lwm hauv quercetin qauv, kuj ntxiv rau nws cov dawb radical scavenging peev xwm [69, 71]. Kev hloov ntawm nws ntau pawg OH pab quercetin sib txawv biochemical thiab pharmacological zog [72]. Nws tau kwv yees tias qhov nruab nrab txhua hnub noj quercetin tuaj yeem yog li 25 mg [20]. Lub bioavailability ntawm quercetin nyob ntawm nws daim ntawv metabolic hauv zaub mov [73]. Quercetin tuaj yeem pom muaj dawb lossis aglycone xeev thiab cov ntaub ntawv sib txuas, uas nws cuam tshuam nrog ntau lub molecules, suav nrog lipids, carbohydrates, cawv, thiab sulfate pawg los tsim nws cov derivatives, suav nrog prenylated quercetin, quercetin ethers, quercetin glycoside, thiab [quercetin sulfate. 72] ib. Hauv cov nroj tsuag, daim ntawv ntawm quercetin yog quercetin glucosides (quercetin-glucose conjugates). Quercetin glucosides dhau los ua hydrolysis los tsim quercetin aglycone tom qab nqus tau hauv apical membrane ntawm enterocytes. Tom qab ntawd, enterocytic transferases metabolize quercetin aglycone rau glucuronidated, sulfonylated, thiab methylated forms [73]. Cov quercetin metabolites thaum thauj mus rau lub siab ua rau lwm cov txheej txheem sib txuas los tsim Que-3- glucuronide thiab quercetin-3′-sulfate [73–75]. Qhov siab tshaj plaws plasma concentration ntawm quercetin txawv ntawm 3.5 mus rau 5.0 μM ib zaug tau absorbed hauv daim ntawv ntawm glucosides. Txawm li cas los xij, nws qhov siab tshaj plaws plasma concentration yog tsawg dua 0.33μM thaum absorbed nyob rau hauv daim ntawv unconjugated, qhia tsawg npaum nqus [76].

Quercetin muaj ntau yam txiaj ntsig rau tib neeg kev noj qab haus huv, suav nrog tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob, tshuaj tiv thaiv kab mob thiab tiv thaiv kab mob, cardioprotective, gastroprotective, thiab kev tiv thaiv kab mob [69, 77]. Nrog rau qhov tshwj xeeb cuam tshuam rau cov qog hlwb thiab tsis muaj kev cuam tshuam rau ib txwm thiab tsis hloov pauv, quercetin tau nyiam ntau tus kws tshawb fawb los tshawb xyuas nws lub peev xwm los ua kom muaj zog oxidative kev nyuaj siab, kev loj hlob, thiab metastasis [78]. Ntau qhov kev tshawb fawb tau pom tias muaj kev cuam tshuam cuam tshuam ntawm quercetin tiv thaiv kab mob pancreatic, plab hnyuv, prostate, ntsws, zes qe menyuam, nasopharyngeal, mis, thiab mob qog noj ntshav [79-85]. Ntau qhov kev tshawb fawb soj ntsuam tsis ntev los no tau tshawb xyuas quercetin cov nyhuv ntawm PC. Hauv qhov no, Liu et al. [86] tau tshawb nrhiav cov teebmeem tiv thaiv kabmob kheesxaws thiab kev ua haujlwm zoo ntawm quercetin hauv GMC-resistant hlwb qog noj ntshav. Hauv daim ntawv ntsuam xyuas no, BxPC-3, PANC-1 thiab HepG2, thiab Huh{14}} kab ntawm tes tau kawm. Kev soj ntsuam kev loj hlob tau nthuav tawm tias quercetin muaj cytotoxic cuam tshuam rau GMC-resistant cell kab nrog rau HepG2 thiab PANC-1, thiab ntws cytometric tsom xam tau qhia txog qhov tseem ceeb ntawm cov txiaj ntsig ntawm cov kab ntawm tes. GMC kev kho mob, nrog rau quercetin, ua rau muaj kev tiv thaiv kab mob ntau ntxiv piv nrog GMC ib leeg, thiab quercetin coj mus rau S theem ntes nyob rau hauv resistant cell kab. Hoca et al. [5] tshawb xyuas cov txiaj ntsig ntawm quercetin thiab resveratrol ntawm epithelial-mesenchymal hloov pauv (EMT) ntawm CD133 ntxiv thiab CD133−mob qog noj ntshav pancreatichlwb. CD133 ntxiv cov hlwb tau txais los ntawm PANC-1 hlwb los ntawm MiniMACS system. CD133 ntxiv thiab CD133- PANC-1 hlwb raug kho nrog ntau qhov sib txawv ntawm resveratrol thiab quercetin. Kev kuaj Immunocytochemistry siv cov tshuaj tiv thaiv xws li TNF- , ACTA-2, N-cadherin, IL-1 , thiab vimentin tau thov rau kev ntsuam xyuas cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob ntawm resveratrol thiab quercetin. Cov txiaj ntsig tau qhia tias kev tiv thaiv kab mob ntawm CD133 ntxiv rau cov hlwb muaj zog dua li ntawm CD{10}} hlwb. ACTA-2, N-cadherin, thiab IL-1 immunoreactivities tau txo qis, hos vimentin thiab TNF- immunoreactivities tau nce hauv quercetin-kho CD133 ntxiv cov hlwb. Tsis tas li ntawd, quercetin tau zoo dua li resveratrol hauv inhibiting metastasis. Guo et al. [87] tau kawm txog kev kho lub peev xwm ntawm quercetin hauv kev tsom sonic hedgehog (SHH) signaling ntawm PDA. Cov teebmeem ntawm quercetin ntawm apoptosis, tsiv teb tsaws, thiab ntxeem tau ntawmmob qog noj ntshav pancreatichlwb (PCCs) tau soj ntsuam hauv PDA xenograft nas qauv. Raws li cov txiaj ntsig, quercetin inhibited PCC proliferation los ntawm down-regulating c-Myc qhia thiab suppressed EMT los ntawm kev txo TGF - 1 qib, uas inhibited PCC tsiv teb tsaws thiab ntxeem tau. Kev kho mob Quercetin txo PDA kev loj hlob thiab metastasis hauv cov qauv liab qab los ntawm kev txo qis SHH kev ua haujlwm. Tsis tas li ntawd, SHH tau qhib TGF- 1/Smad2/3 signaling thiab txhawb EMT los ntawm inducing qhov kev qhia ntawm Snail1and Zeb2 uas instigated ib nrab reversal ntawm quercetin-mediated inhibition ntawm PCC tsiv teb tsaws thiab ntxeem tau.

4.1. Molecular Mechanisms hauv qab Quercetin-Mediated Efffects hauv Cancer

4.1.1. Kev cuam tshuam hauv Autophagy thiab Apoptosis Induction. Raws li Pang et al. [88], quercetin tuaj yeem cuam tshuam rau CD36 thiab txo qhov kev tuag ntawm PC los ntawm kev txhawb nqa cov roj fatty acids, txhim kho cell adhesion, txhawb kev tiv thaiv kab mob, thiab tswj thrombospondin-1. Tsis tas li ntawd, cov qauv yav dhau los qhia tau hais tias quercetin muaj cov haujlwm pro-apoptotic hauv kev tawm tsam Bcl -2 protein thiab hauv kev txhawb nqa p53 noob; Txawm li cas los xij, inhibition ntawm Bcl -2 transcription tuaj yeem tiv thaiv kev loj hlob ntawm cov qog [12]. Hauv kev tshawb fawb piv txwv, Serri et al. [89], tau tshawb xyuas cov nyhuv ntawm GMC nrog biodegradable nanoparticles (NPs) loaded nyob rau hauv quercetin ntawm PC cell kab. Cov khoom tsim NPs dai kom zoo nkauj nrog hyaluronic acid (HA) thiab thauj khoom nrog quercetin thiab GMC nthuav tawm cytotoxicity ntawm PANC-1 thiab Mia-PaCa-2 cov kab ntawm tes thaum piv nrog cov tshuaj liab qab thiab NPS uas tsis yog kho nrog HA ntawm qhov chaw. Cov txiaj ntsig tau qhia tias NPS nthuav tawm HA tuaj yeem txhim kho cov haujlwm tiv thaiv kab mob ntawm Que, uas ua rau txo qis ntawm interleukin (IL) qhia qib hauv cov kab ntawm tes thiab ua ntej nce nrog lipopolysaccharides (LPS). Hauv lwm qhov kev tshawb fawb, Lan et al. [90] pom tau tias quercetin accelerates cell tuag thiab chemosensitivity ntawm tib neeg PC hlwb. Cov txiaj ntsig tau pom tias kev ntsiag to ntawm cov receptor rau cov khoom lag luam siab glycation kawg (RAGE) los ntawm RAGE-specific siRNA intensified autophagy thiab apoptosis los ntawm suppressing PI3K / AKT / mTOR axis hauv MIA Paca -2 thiab GMC-resistant hlwb (MIA Paca -2 GMCR hlwb). Tsis tas li ntawd, quercetin txo RAGE qhia thiab ua kom yooj yim rau apoptosis, autophagy, thiab chemosensitivity rau GMC hauv MIA Paca-2 GMCR hlwb, uas qhia tias ntxiv cytotoxicity tau ua tiav los ntawm kev sib ntxiv ntawm quercetin hauv kev kho nrog GMC. Yus et al. [91] pom tias quercetin pib ua haujlwm inhibitory tiv thaiv PATU-8988 thiab PANC{25}} hlwb thiab txo qis kev tso tawm ntawm matrix metalloproteinase (MMP). Hauv txoj kev tshawb no, lawv tau siv STAT-3 thiab IL-6 ua kom pom tseeb qhov cuam tshuam ntawm kev kho quercetin ntawm cell malignancy. MMP secretion thiab epithelial-mesenchymal hloov pauv (EMT) txhawb nqa STAT-3 txoj kev taw qhia, thaum quercetin thim rov qab IL-6-induced EMT thiab ntxeem tau. Raws li kev tshawb pom tseem ceeb, txoj kev tshawb fawb no tau pom tias quercetin yog tus neeg sawv cev zoo hauv PC kev kho mob vim nws thaiv STAT-3 txoj kev taw qhia, ua rau muaj kev tawm tsam ntawm EMT thiab metastasis. Tsis tas li ntawd, Nwaeburu et al. [92] tau tshawb nrhiav cov txiaj ntsig ntawm quercetin ntawm miRNA kev qhia hauv PC hlwb thiab xaus lus tias kev kho quercetin ua rau muaj kev qhia ntawm miR- 200b-3p hauv AsPC1 kab ntawm tes, uas muaj lub luag haujlwm tseem ceeb hauv qhov tsis xwm yeem. Kev faib tawm ntawm PDA hlwb los ntawm kev taw qhia cov cim qhia (Daim duab 2).

4.1.2. Kev cuam tshuam hauv kev loj hlob thiab kev loj hlob ntawm tes. Inhibition ntawm PC cell proliferation yuav qhia tau hais tias ib tug txawv mechanism ntawm anticancer teebmeem ntawm quercetin (Table 2). Hauv qhov no, Pham et al. [93] tau kawm txog cov txiaj ntsig ntawm quercetin ntawm dysregulated epigenetic nyeem, suav nrog bromodomain thiab ntxiv terminal domain (BET) cov proteins, hauv vitro thiab xenograft qauv ntawm PC. Raws li cov txiaj ntsig, tom qab kev kho mob nrog BET inhibitors thiab quercetin, qhov kev loj hlob thiab kev tsim muaj peev xwm ntawm cov qog nqaij hlav cancer tau txo qis, thiab apoptosis stimulated. Tsis tas li ntawd, quercetin txo qis cov protein ntau ntawm hnRNPA1 uas tswj hwm mRNA kev txhais lus thiab xa tawm cov proteins antiapoptotic, hauv vivo, thiab nce BET inhibitor cov teebmeem ntawm suppressing hlwb proliferation thiab qog loj hlob. Hauv lwm txoj kev tshawb fawb, Nwaeburu et al. [94] tshawb nrhiav quercetin cuam tshuam rau PC cell proliferation los ntawm kev ua kom muaj Notch-inhibitor Numbl raws li kev cia-7c hom phiaj. Hauv vivo xenotransplantation ntawm PDA cell thiab tom qab IV txhaj tshuaj ntawm let-7c provoked ib tug noteworthy txo cov qog loj nyob rau hauv lub fertilized qaib qe qauv. Immunohisto chemistry tsom xam pom tau tias cia -7c upregulated Numbl thiab reserved Notch thiab nce qib. Cov kev tshawb pom qhia tau hais tias Que-induced cia-7c txo cov qog nqaij hlav qog noj ntshav thiab cov qog loj hlob.

4.1.3. Kev cuam tshuam hauv Oxidative Stress. Redox homeostasis tseem ceeb heev rau kev ua haujlwm ntawm tes thiab ROS muaj lub luag haujlwm tseem ceeb hauv kev xa xov tooj ntawm tes. Txawm li cas los xij, kev cuam tshuam hauv cov kab mob antioxidant tuaj yeem ua rau ntau dhau ntawm cov cellular ROS, xws li hydroxy dawb radicals thiab H2O2 [95]. ROS ntau dhau ntawm cov cell ua rau oxidative puas tsuaj rau ntau yam macromolecules lom uas muaj lipids, proteins, thiab cov khoom siv caj ces, ua rau muaj kab mob, xws li mob qog noj ntshav, o, atherosclerosis, angiogenesis, thiab kev laus [96-100]. Yog li ntawd, kev pab cov hlwb kom redox homeostasis yog qhov muaj txiaj ntsig zoo, uas tuaj yeem muab tau los ntawm kev noj cov khoom noj khoom haus ntuj, xws li Que.

Nrog rau ntau OH pawg thiab conjugated π orbitals tso cai rau nws pub hydrogen lossis electrons, thiab yog li tshem tawm superoxide anion (•O2−) thiab H2O2. Quercetin yog suav tias yog ib qho zoo tshaj plaws dawb-radical scavenging antioxidant [101]. Querce tin tuaj yeem tsim cov semi-quinone radical thiab H2O2 los ntawm cov tshuaj tiv thaiv nrog •O2-, thaum tseem txo qis H2O2 qib nyob rau hauv lub xub ntiag ntawm peroxidases thiab ua kom cov hlwb tiv thaiv H2O2 puas [64]. Lub semi-quinone yog ib qho ntawm cov khoom muaj txiaj ntsig zoo oxidation thiab ua tiav cov tshuaj tiv thaiv oxidation thib ob nrog Que, tsim cov quinone ntxiv (Que-Quinone; QQ) [64]. QQ yog tus ua txhaum rau lipid peroxidation nrog rau cov protein thiab DNA puas tsuaj nrog ntau dua affinity rau react nrog lipids, proteins, thiab DNA [64, 102]. QQ nrog siab reactivity ntawm thiols yuav arylate protein thiols, impairing ob peb enzymes tseem ceeb; Txawm li cas los xij, nws tsim cov glutathione uas ruaj khov (GSH)-oxidized adducts suav nrog 8-glutathionyl-quercetin (8-GSQ), 6-glutathionyl-quercetin (6-GSQ), thiab 2 '-glutathionyl-quercetin (2'-GSQ) thaum txo GSH tshwm sim [103, 104]; Cov tshuaj tiv thaiv no yog thim rov qab thiab glutathionyl-quercetin adducts tuaj yeem cuam tshuam tas li rau hauv QQ thiab GSH [105]. Yog li ntawd, siab GSH concentrations nyob rau hauv lub hlwb, oxidized quercetin cov ntaub ntawv GSQ los ntawm cov tshuaj tiv thaiv nrog GSH, neutralizing lub toxicity ntawm QQ. Txawm li cas los xij, oxidized quercetin reacts nrog cov protein thiols thaum qis qis ntawm GSH muaj nyob hauv cov hlwb, qhia txog cov nyhuv prooxidant ntawm quercetin [105, 106]. Yog li ntawd, GSH concentration hauv hlwb txiav txim siab seb cov nyhuv antioxidant ntawm quercetin tuaj yeem kov yeej nws cov txiaj ntsig pro-oxidant. Tseeb, qib siab ntawm GSH txwv quercetin cytotoxicity thiab tso cai rau nws los qhia nws cov haujlwm antioxidant tab sis tsis yog prooxidant kev ua haujlwm [107]. Tsis tas li ntawd, nws tau pom tias quercetin induces GSH synthesis [108, 109]. Tsis tas li ntawd, quercetin tseem ua haujlwm antioxidant los ntawm kev ua kom lub cev muaj zog erythroid 2-txog yam 2 (Nrf2) nrog rau nws cov hom phiaj nqes hav, uas yog ib qho tseem ceeb rau kev tswj cov cell redox hemostasis [110, 111].

4.1.4. Kev cuam tshuam hauv Epithelial-to-Mesenchymal Transition (EMT). Cov txheej txheem physiological, kev hloov pauv ntawm epithelial-rau-mesenchymal (EMT), muaj lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tus tsiaj embryonic thiab cell thiab cov ntaub so ntswg sib npaug; Txawm li cas los xij, nws tseem muaj lub luag haujlwm tseem ceeb hauv cov qog nqaij hlav thiab qog nqaij hlav [112]. Thaum lub sij hawm EMT, cov hlwb epithelial tau txais qee qhov kev hloov pauv suav nrog kev poob ntawm cov cellular polarity, cuam tshuam kev sib txuas ntawm cov hlwb thiab cov nplaum sib txuas, thiab tau txais kev nkag mus thiab tsiv teb tsaws chaw [113, 114]. EMT tuaj yeem saib xyuas los ntawm cov cim protein, suav nrog E- thiab N-cadherin, Snail, thiab Vimentin [114, 115]. Tsis tas li ntawd, MMPs ze ze rau EMT yog tsis ntev los no tau qhia ua EMT cov cim thiab ua qhov tseem ceeb rau nws, muab qhov tsim nyog rau cov qog infiltration thiab metastasis los ntawm degrading lub extracellular matrix (ECM) thiab hauv qab daus membrane (BM) nyob ze ntawm lub qog sab nrauv [116. , 117] ib. Qhov cuam tshuam ntawm quercetin ntawm EMT hauv PC hlwb tau tshawb xyuas los ntawm ob peb txoj kev tshawb fawb. Hauv ib txoj kev tshawb fawb, nws tau pom tias kev kho quercetin tuaj yeem txo EMT thiab MMP tso tawm hauv PATU-8688 PC cell kab [91]. Quercetin txo mRNA thiab protein qhia theem ntawm N-cadherin, Slug, Vimentin Zeb1, Twist, thiab Snail, qhia txog lub peev xwm ntawm quercetin kom thim rov qab cov txheej txheem EMT; Txawm li cas los xij, nws nce E-cadherin qhia [91]. Quercetin kuj inhibited MMP2 thiab MMP7 protein qhia [91]. Dhau li ntawd, nws tau raug qhia tias quercetin exerted nws inhibitory cuam tshuam rau EMT, ntxeem tau, thiab metastasis hauv PC hlwb los ntawm suppressing STAT-3 signaling pathway [91]. Lwm txoj kev tshawb fawb pom tau tias quercetin txwv EMT los ntawm suppressing SHH thiab TGF- / Smad signaling pathways, koom nrog txhawb EMT los ntawm induction ntawm Zeb2 thiab Snail1 kab lus [87]. Quercetin downregulated Vim (encoding vimentin) thiab Acta2 (encoding -SMA) gene expressions, thiab upregulated Cdh1 (encoding E-cadherin) noob qhia hauv PANC-1 thiab Patu8988 hlwb; raws li kev kho quercetin, cov qib protein ntawm hom I collagen, N-cadherin, -SMA, thiab vimentin raug txo; Txawm li cas los xij, qib protein ntawm E-cadherin tau nce hauv hlwb [87]. Quer cetin txo TGF- 1 kev qhia thiab ntawm EMT-TFs (EMT-inducing transcription factor) Snail1 thiab Zeb2 [87]. EMT-TFs (Snail1 thiab Zeb2) yog lub hom phiaj tseem ceeb hauv qab ntawm TGF- 1/Smad2/3 signaling pathway suppressing E cadherin expression [118, 119]. Tsis tas li ntawd, qhov kev hloov pauv hauv nuclear thiab phosphorylation ntawm Smad2 thiab Smad3 kuj raug txwv los ntawm quercetin [87]. Nws tau raug tshaj tawm tias thaum ua haujlwm los ntawm TGF- 1 thiab tsim cov heteromeric complexes nrog Smad4, Smad2 thiab Smad3 hloov mus rau lub nucleus thiab ntxias EMT-TFs 'kev qhia [120]. Nws kuj tau qhia tias quercetin tuaj yeem cuam tshuam EMT hauv PC qia hlwb los ntawm kev tawm tsam ntawm N-cadherin [5]. Quercetin downregulated Twist2 qhia, cov protein koom nrog EMT, hauv PC qia hlwb [121], tawm tswv yim EMT inhibition los ntawm quercetin [122].

4.1.5 ib. Kev cuam tshuam hauv Chemo-Sensitivity. Los ntawm kev txhim kho kev ua tau zoo hauv kev sib xyaw nrog lwm cov khoom noj khoom haus, quercetin tau raug tshawb xyuas los ua ib qho kev cog lus ntxiv los ua kom muaj txiaj ntsig ntawm ntau cov kws khomob [122, 123]. Lan, Chen, Kuo, Lu, thiab Yen [90] tau qhia tias quercetin tuaj yeem txo qis cell viability, txhawb autophagy, thiab nce apoptosis los ntawm suppressing receptors rau qib siab glycation kawg cov khoom (RAGE) hauv GMC-resistant PC hlwb, muaj kev cuam tshuam ntau dua ib zaug. nrog GMC. Cov txiaj ntsig tau tshaj tawm tias RAGE silencing txhawb nqa GMC-induced cytotoxicity hauv MIA Paca -2 thiab MIA Paca -2 GEMR hlwb ntawm PI3K / AKT / mTOR axis [90]. Raws li RAGE silencing, quercetin txo qhov kev qhia ntawm RAGE, uas ua rau lub voj voog ntawm tes raug ntes, apoptosis, autophagy, thiab txhawb nqa GEM kev ua tau zoo hauv MIA Paca -2 GEMR hlwb [90], thov quercetin ua ib qho kev txhim kho ntawm kev siv tshuaj khomob ntawm cov tshuaj. tawm tsam PC. Hauv lwm txoj kev tshawb fawb, quercetin txhawb cov qog necrosis yam cuam tshuam txog apoptosis-inducing ligand (TRAIL)-induced apoptosis hauv TRAIL-resistant PC cells [124], thiab txo qis cellular FLICE-zoo li inhibitory protein (cFLIP) qhia, thaum ua rau c-Jun N. -terminal kinase (JNK), ua rau cov proteasomal degradation ntawm cFLIP thiab nws thiaj li ua rau PC hlwb raug mob rau TRAIL-induced apoptosis [124]. Nws kuj tau tshaj tawm tias quercetin txo qis kev ua tau zoo ntawm PC cell kab nrog rau PANC-1, MiaPaCa- 2, thiab BxPC-3 [125, 126]. Ib zaug ua ke nrog lwm cov kws khomob, xws li GMC lossis 5-FU, quercetin tuaj yeem cuam tshuam rau kev siv tshuaj khomob raws li cov xovtooj ntawm tes siv, xws li txhawm rau tiv thaiv kev loj hlob ntawm lossis tsis muaj teebmeem rau cov qog nqaij hlav [125, 126]. Borska et al. [127] qhia tias quercetin induced apoptosis thiab suppressed cell proliferation nyob rau hauv ob qho tib si daunorubicin-sensitive EPP 85-181P thiab resistant EPP85-181 RDB PC cell kab. Quercetin muaj kev sib koom ua ke nrog daunorubicin hauv ob lub hlwb rhiab thiab resistant [127]. Lawv kuj tau qhia tias kev kho quercetin tuaj yeem txo P-glycoprotein qhia [128].

5. Cov lus xaus

Kev noj zaub mov ua ke nrog cov tshuaj kho tau raug suav tias yog tus yuam sij rau kev kho mob ntawm ntau yam kab mob, suav nrog mob qog noj ntshav. Cov kev kho mob zoo li cov khoom siv ntuj tsim dua li lwm txoj kev kho mob vim lawv cov nqi qis dua thiab cov kev mob tshwm sim tau nce ntxiv los ntawm cov kws tshawb fawb. Tshwj xeeb, quercetin ua rau muaj kev tiv thaiv kab mob qog noj ntshav rau PC hlwb los ntawm kev kho apoptosis, tab sis cov kev tshawb fawb tsis ntev los no kuj tau qhia tias quercetin cuam tshuam rau ntau yam kev hloov pauv ntawm cov teeb liab los txo kev mob qog noj ntshav. Quercetin inhibits qhov kev qhia ntawm N-cadherin, MMP-9, STAT-3 kev taw qhia txoj hauv kev thiab muaj feem cuam tshuam EMT, ntxeem tau, thiab metastasis. Quercetin txhim kho gemcitabine chemosensitivity hauvmob qog noj ntshav pancreatichlwb los ntawm inhibitory nyhuv ntawm RAGE qhia. Lub caij no, nws muaj kev nkag tau yooj yim, ua tau zoo, thiab tsis muaj toxicity piv nrog rau lwm cov kev tshawb fawb tebchaw, ua rau nws ua tus neeg sawv cev txaus siab hauv kev kho mob qog noj ntshav. Tsis ntev los no, quercetin tau raug qhia thiab siv los ua cov tshuaj cog lus hauv kev kho mob qog noj ntshav ib leeg lossis ua ke nrog lwm cov tshuaj kws khomob. Cov kev tshawb fawb soj ntsuam zoo yav tom ntej yog xav tau los pab cov kws tshawb fawb los ntsuas kev nyab xeeb thiab muaj peev xwm ntawm quercetin tiv thaiv PC.

Parina Asgharian, 1,2 Abbas Pirpour Tazehkand, 3 Saiedeh Razi Soofiyani, 4,5 Kamran Hosseini, 6,7 Miquel Martorell, 8 Vahideh Tarhriz, 5 Hossein Ahangari, 9 Natália Cruz-Martins , 10,11-12 Javad , 13 Zainab M. Almarhoon , 14 Alibek Ydyrys, 15 Ablaikhanova Nurzhanyat, 16 Arailym Yessenbekova, 16 thiab William C. Cho 17
1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Pharmacognosy, Kws Qhia Ntawv ntawm Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Biochemistry thiab Clinical Laboratories, Kws Qhia Ntawv ntawm Tshuaj, Tabriz University of Medical Sciences, Tabriz, Iran
4 Clinical Research Development Unit ntawm Sina Educational, Research thiab Treatment Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
6 Pawg Neeg Tshawb Fawb Txog Tub Ntxhais Kawm, Shiraz University of Medical Sciences, Shiraz, Iran
7 Lub Tsev Haujlwm Saib Xyuas Tshuaj Molecular, Kws Qhia Ntawv ntawm Kev Tshawb Fawb Txog Kev Kho Mob thiab Kev Tshawb Fawb, Shiraz University of Medical Sciences, Shiraz, Iran
8 Department of Nutrition and Dietetics, Kws Qhia Ntawv ntawm Pharmacy thiab Center for Healthy Living, University of Concepción, 4070386 Concepción, Chile
9 Department of Food Science thiab Technology, Kws qhia ntawv ntawm Khoom noj khoom haus thiab Khoom noj khoom haus Science, Tabriz University of Medical Sciences, Tabriz, Iran
10 Department of Biomedicine, Kws Qhia Ntawv ntawm Tshuaj, University of Porto, Alameda Prof. Hernâni Monteiro, Porto, Portugal 11Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal
12 Lub Tsev Kawm Ntawv ntawm Kev Tshawb Fawb thiab Kev Kawm Qib Siab hauv Kev Tshawb Fawb Txog Kev Noj Qab Haus Huv thiab thev naus laus zis (CESPU), Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
13 Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
14 Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia
15Biomedical Research Center, Al-Farabi Kazakh National University, Al-Farabi Av. 71, 050040 Almaty, Kazakhstan
16 Department of Biophysics, Biomedicine thiab Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Av. 71, 050040 Almaty, Kazakhstan
17 Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong, Suav

Cov ntawv xov xwm yuav tsum tau hais rau Vahideh Tarhriz; t.tarhriz@yahoo.com, Hossein Ahangari; ahangaryhossein.tbzmed73@gmail.com, Javad Sharifi-Rad; javad.sharififirad@gmail.com, thiab William C. Cho; chocs@ha.org.hk
Tau txais 8 Lub Xya Hli 2021; Hloov kho 9 Cuaj hlis 2021; Tau txais 16 Lub Kaum Hli 2021; Tshaj tawm rau lub Kaum Ib Hlis 3, 2021
Academic Editor: Felipe L. de Oliveira
Copyright © 2021 Parina Asgharian li al. Qhov no yog ib tsab xov xwm qhib nkag tau muab faib raws li Creative Commons Attribution License, uas tso cai rau kev siv tsis txwv, kev faib tawm, thiab luam tawm hauv ib qho nruab nrab, yog tias cov haujlwm qub raug suav hais tias yog.

Cov ntaub ntawv muaj

Cov ntaub ntawv siv los txhawb qhov kev tshawb pom ntawm qhov kev tshawb fawb no yog muaj los ntawm tus kws sau ntawv raws li kev thov.

Kev tsis sib haum xeeb

Cov kws sau ntawv tshaj tawm tsis muaj kev sib tw nyiam.

Cov neeg sau ntawv koom tes

Parina Asgharian thiab Abbas Pirpour Tazehkand tau pab tib yam rau txoj haujlwm no.

Kev lees paub

Cov kws sau ntawv lees paub lub Chaw Tshawb Fawb Tshuaj Molecular, Bio-Medicine Institute, Tabriz University of Medical Sciences, thiab Kev Tshawb Fawb Kev Tshawb Fawb Kev Tshawb Fawb ntawm Sina Educational, Kev Tshawb Fawb thiab Kev Kho Mob, Tabriz University of Medical Sciences, Tabriz, Iran. Txoj haujlwm no tau txais kev txhawb nqa thiab nyiaj txiag los ntawm Tabriz University of Medical Sciences, Tabriz, Iran (tus lej nyiaj pab: 68344).

Cov ntaub ntawv

[1] JD Mizrahi, R. Surana, JW Valle, thiab RT Shroffff, "Pancreatic cancer," The Lancet, vol. 395, Nr. 10242, p. 2008–2020, 2020.
[2] F. Bray, J. Ferlay, I. Soerjomataram, RL Siegel, LA Torre, thiab A. Jemal, "Global cancer statistics 2018: GLOBOCAN kwv yees qhov xwm txheej thiab kev tuag thoob ntiaj teb rau 36 mob qog noj ntshav hauv 185 lub teb chaws," CA: a Cancer Journal for Clinicians, vol. 68, Nr. 6, nr 394–424, 2018.
[3] RL Siegel, KD Miller, thiab A. Jemal, "Cancer statistics, 2016," CA: Cancer Journal for Clinicians, vol. 66, Nr. 1, p.m. 7–30, 2016.
[4] A. Scarpa, FX Real, thiab C. Luchini, "Cov noob caj noob ces ntawm kev sib koom ua ke ntawm pancreatic adenocarcinomas thiab IPMNs cam tam sim no views ntawm kev tswj xyuas kev kho mob," Gut, vol. 6 7, nr. 9, pp. 1561–1563, 2018.
[5] M. Hoca, E. Becer, H. Kabadayı, S. Yücecan, thiab HS Vatansever, "Cov nyhuv ntawm resveratrol thiab quercetin ntawm epithelial-mesenchymal hloov nyob rau hauv pancreatic cancer qia cell," Nutrition and Cancer, vol. 7 2, nr. 7, nr 1231–1242, 2020.
[6] A. Vafadar, Z. Shabaninejad, A. Movahedpour, et al., "Quercetin thiab mob qog noj ntshav: kev nkag siab tshiab rau nws cov kev kho mob ntawm zes qe menyuam qog noj ntshav," Cell & Bioscience, vol. 10, pp. 1–17, 2020.
[7] SM Nabavi, D. Šamec, M. Tomczyk, et al., "Flavonoid biosynthetic pathways nyob rau hauv cov nroj tsuag: ntau yam hom phiaj rau metabolic engineering," Biotechnology Advances, vol. 38 Ib., p. 10 7316, 2020.
[8] A. Scarano, M. Chieppa, thiab A. Santino, "Saib ntawm flavonoid biodiversity nyob rau hauv horticultural qoob loo: ib tug coloured mine nrog cov kev pab cuam noj haus," Nroj tsuag, vol. 7, nre. 4 ib,p. Peb Hlis 98, 2018.
[9] A. Durazzo, M. Lucarini, EB Souto, et al., "Polyphenols: ib tug txheej txheem cej luam ntawm chemistry, tshwm sim, thiab tib neeg noj qab haus huv," Phytotherapy Research, vol. 3 3, nr. 9 Ib., 2221–2243, 2019.
[10] DM Kopustinskiene, V. Jakstas, A. Savickas, and J. Bernatoniene, "Flavonoids as anticancer agents," Nutrients, vol. 12, nr. 2 ib,p. 457 Peb 2020.
[11] WM Dabeek thiab MV Marra, "Kev noj zaub mov quercetin thiab kaempferol: bioavailability thiab muaj peev xwm mob plawv-txog bioactivity hauv tib neeg," Nutrients, vol. 11, nr. 10 ib,p. 2288 Peb 2019.
[12] A. Davoodvandi, M. Shabani Varkani, CC Clark, thiab S. Jafarnejad, "Quercetin as an anticancer agent: focus on esophageal cancer," Journal of Food Biochemistry, vol. 4 4, nr. 9, xov e13374, 2020.
[13] B. Salehi, L. Machin, L. Monzote, et al., "Kev kho muaj peev xwm ntawm quercetin: kev pom tshiab thiab kev xav rau tib neeg noj qab haus huv," ACS Omega, vol. 5, nre. 20 Ib., 11849–11872, 2020.
[14] SR Soofifiyani, K. Hosseini, H. Forouhandeh, et al., "Quercetin as a new therapeutic approach for lymphoma," Oxidative Medicine and Cellular Longevity, vol. Peb 2021, 15, 2021.
[15] R. Shafabakhsh thiab Z. Asemi, "Quercetin: ib tug natural compound rau kev kho mob ntawm zes qe menyuam," Phau ntawv Journal ntawm zes qe menyuam tshawb fawb, vol. 12, nr. 1, pp. 1–9, 2019.
[16] S. Bhagat, M. Rathore, S. Kachhwaha, thiab HK Sharma, "Kev tshuaj xyuas Phytochemical, kev txiav txim siab ntawm tag nrho cov ntsiab lus phenol, tag nrho cov ntsiab lus flavonoid thiab kev kwv yees ntau ntawm Rutin thiab quercetin siv RP-HPLC hauv cov txiv hmab txiv ntoo ntawm Capparis decidua ( Forsk.) Edgew. Ind. J. Pure app," Biosci, vol. 9 Ib., 254–261, 2021.
[17] Y. Zeng, Y. Li, J. Yang, et al., "Kev kho lub luag haujlwm ntawm cov khoom siv hauv cov khoom siv rau kev tiv thaiv kab mob ntev hauv tib neeg," Cov ntaub ntawv pov thawj-raws li Complementary thiab Alternative Medicine, vol. Xyoo 2017, 13 nplooj ntawv, 2017.
[18] M. Górecki thiab E. Hallmann, "Cov ntsiab lus antioxidant ntawm kas fes thiab nws cov kev ua hauv vitro ua ib qho txiaj ntsig ntawm nws txoj kev tsim khoom thiab lub sijhawm ci thiab brewing," Antioxidants, vol. 9, nre. 4 ib,p. Peb Hlis 308, 2020.
[19] AMO Amoussa, L. Zhang, C. Lagnika, et al., "Qhov cuam tshuam ntawm kev ua ntej cua sov thiab ziab ntawm pyridoxine, phenolic tebchaw, ginkgolic acids, thiab antioxidant muaj peev xwm ntawm Ginkgo biloba txiv ntseej," Journal of Food Science, vol. 86, nr. 9 Ib., 4197–4208, 2021.
[20] M. Harwood, B. Danielewska-Nikiel, J. Borzelleca, G. Flamm, G. Williams, thiab T. Kab, "Kev tshuaj xyuas tseem ceeb ntawm cov ntaub ntawv ntsig txog kev nyab xeeb ntawm quercetin thiab tsis muaj pov thawj ntawm {{ 2}}nyob rau hauv vivo_ toxicity, nrog rau tsis muaj genotoxic/carcinogenic zog," Khoom noj khoom haus thiab tshuaj toxicology, vol. 4 5, nr. 11, pp. 2179–2205, 2007. [21] RS Mateos thiab KC Conlon, “Pancreatic cancer,” Surgery (Oxford), vol. 34, Nr. 6, pp. 282–291, 2016.
[22] CE DeSantis, J. Ma, A. Goding Sauer, LA Newman, thiab A. Jemal, "Kev txheeb xyuas mob qog noj ntshav mis, 2017, haiv neeg tsis sib xws hauv kev tuag los ntawm lub xeev," CA: Phau Ntawv Xov Xwm Cancer for Clinicians, vol. 6 7, nr. 6, pp. 439–448, 2017.
[23] L. Rahib, BD Smith, R. Aizenberg, AB Rosenzweig, JM Fleshman, thiab LM Matrisian, "Tshaj tawm kev mob qog noj ntshav thiab tuag rau 2030: lub nra hnyav ntawm cov thyroid, siab, thiab mob qog noj ntshav hauv Tebchaws Meskas," Cancer Research, vol. 7 4, nr. 11, pp. 2913–2921, 2014.

[24] M. Hidalgo, "Pancreatic cancer," New England Journal of Medicine, vol. 362, Nr. 17, pp. 1605–1617, 2010.
[25] P. Maisonneuve, "Epidemiology thiab lub nra ntawm pancreatic cancer," La Presse Médicale, vol. 48, Nr. 3, p. e113–e123, 2019.
[26] P. Ramakrishnan, WM Loh, SC Gopinath, et al., "Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer," Acta Pharmaceutica Sinica B, vol. 10, nr. 3 Ib., 399–413, 2020.
[27] J. Huang, V. Lok, CH Ngai, et al., "Tag nrho lub nra ntawm lub ntiaj teb no, kev pheej hmoo rau, thiab tiam sis nyob rau hauv pancreatic cancer," Gastroenterology, vol. 160, Nr. 3, pp. 744–754, 2021. [28] S. Shore, M. Raraty, P. Ghaneh, and J. Neoptolemos, "Chemotherapy for pancreatic cancer," Alimentary Pharmacology & Therapeutics, vol. 18, nr. 11-12, p. 1049–1069, 2003.
[29] SR Boreddy thiab SK Srivastava, "Pancreatic cancer chemoprevention by phytochemicals," Cancer Letters, vol. 334, Nr. 1, p. 86–94, 2013.
[30] MM Manson, "Kev tiv thaiv kab mob qog noj ntshav - lub peev xwm rau kev noj zaub mov kom hloov pauv cov teeb liab molecular," Trends in Molecular Medicine, vol. 9, nre. 1, pp. 11–18, 2003.
[31] P. Knekt, J. Kumpulainen, R. Järvinen, et al., "Flavonoid kom tsawg thiab pheej hmoo ntawm cov kab mob," American Journal of Clinical Nutrition, vol. 7 6, nr. 3, pp. 560–568, 2002.
[32] . Phau ntawv Journal of Basic Medical Sciences, vol. 24 Ib., p. Peb 175, 2021.
[33] NJ Tuam Tsev, T. Wilson, thiab DR Jacobs Jr., Kev Noj Qab Haus Huv Kev Noj Qab Haus Huv: Cov Tswv Yim rau Kev Tiv Thaiv Kab Mob, Springer Science & Kev Lag Luam Xov Xwm, 2012.
[34] RH Liu, "Cov txiaj ntsig kev noj qab haus huv ntawm cov txiv hmab txiv ntoo thiab zaub yog los ntawm kev ntxiv thiab kev sib koom ua ke ntawm phytochemicals," American Journal of Clinical Nutrition, vol. 78 ,nr. 3, nr 517-520S, 2003.
[35] JM Pezzuto, "Nroj tsuag-derived anticancer agents," Biochemical Pharmacology, vol. 5 3, nr. 2, pp. 121–133, 1997.
[36] BB Aggarwal, AB Kunnumakkara, KB Harikumar, ST Tharakan, B. Sung, and P. Anand, "Muaj peev xwm ntawm spice-derived phytochemicals rau kev tiv thaiv mob qog noj ntshav," Planta Medica, vol. 7 4, nr. 13, pp. 1560–1569, 2008.
[37] Y.-J. Surh, "Cancer chemoprevention with dietary phytochemicals," Nature Reviews Cancer, vol. 3, nre. 10 Ib., 768–780, 2003.
[38] DR Mans, AB Da Rocha, thiab G. Schwartsmann, "Kev tshawb nrhiav tshuaj tiv thaiv kab mob qog noj ntshav thiab kev loj hlob hauv Brazil: lub hom phiaj cog qoob loo raws li lub tswv yim tsim nyog kom tau txais cov neeg sib tw tiv thaiv kab mob," The Oncologist, vol. 5, nre. 3 Ib., 185–198, 2000.
[39] J. Wang, R. Zhu, D. Sun et al., "Intracellular uptake ntawm curcumin-loaded khoom lipid nanoparticles nthuav tawm cov kev ua ub no zoo tshaj rau cov curcumin los ntawm NF-κB signaling pathway," Phau ntawv Journal of Biomedical Nanotechnology, vol. 11, nr. 3, pp. 403–415, 2015.
[40] S. Fazel Nabavi, R. Thiagarajan, L. Rastrelli li al., "Curcumin: ib yam khoom ntuj rau ntshav qab zib thiab nws cov teeb meem," Cov ntsiab lus tam sim no hauv Tshuaj Kho Mob, vol. 15, nr. 23, pp. 2445–2455, 2015.