槲皮素逆轉乳腺癌阿霉素耐藥及其機制研究

槲皮素逆轉乳腺癌阿霉素耐藥及其機制研究槲皮素逆轉乳腺癌阿霉素耐藥及其機制研究

摘要：阿霉素是一種常用的抗癌藥物，但長期使用后易產(chǎn)生耐藥現(xiàn)象，嚴重影響其療效。槲皮素是一種來自于橡樹科植物的天然化合物，具有抗炎、抗氧化、抗腫瘤等活性。本研究旨在探究槲皮素對乳腺癌細胞所致的阿霉素耐藥性逆轉作用以及其機制。通過細胞實驗和分子生物學技術，發(fā)現(xiàn)槲皮素可顯著增強乳腺癌細胞對阿霉素的敏感性，且槲皮素與阿霉素聯(lián)合使用可顯著抑制乳腺癌細胞的增殖和轉移；同時，槲皮素可通過下調P-gp、BCRP等耐藥相關蛋白的表達，抑制腫瘤細胞的耐藥性。此外，槲皮素還可逆轉EMT過程，從而抑制乳腺癌細胞的惡性程度。綜上所述，槲皮素可作為乳腺癌治療中的潛在逆轉耐藥藥物，為乳腺癌治療提供了新的思路和方向。

關鍵詞：槲皮素；阿霉素耐藥；乳腺癌；P-gp；EMT

Abstract:Doxorubicinisacommonantineoplasticdrug,butlong-termusecaneasilyproducedrugresistance,seriouslyaffectingitstherapeuticeffect.Quercetinisanaturalcompoundfromthefamilyofoakplants,withanti-inflammatory,antioxidant,anti-tumorandotheractivities.Thepurposeofthisstudyistoexplorethereversaleffectofquercetinondoxorubicinresistanceinbreastcancercellsanditsmechanism.Throughcellexperimentsandmolecularbiologytechniques,itwasfoundthatquercetincansignificantlyenhancethesensitivityofbreastcancercellstodoxorubicin,andthecombinationofquercetinanddoxorubicincansignificantlyinhibittheproliferationandmetastasisofbreastcancercells.Meanwhile,quercetincandown-regulatetheexpressionofresistance-relatedproteinssuchasP-gpandBCRP,therebyinhibitingthedrugresistanceoftumorcells.Inaddition,quercetincanreversetheEMTprocess,therebyinhibitingthemalignancyofbreastcancercells.Insummary,quercetincanserveasapotentialdrugtoreversedrugresistanceinbreastcancertreatment,providingnewideasanddirectionsforbreastcancertreatment.

Keywords:Quercetin;Doxorubicinresistance;Breastcancer;P-gp;EMBreastcancerisoneofthemostcommonmalignanttumorsinwomen.Oneofthemajorchallengesinbreastcancertreatmentisdrugresistance.Doxorubicin,acommonlyusedchemotherapeuticdruginbreastcancertreatment,oftenfacesdrugresistancewhichleadstotreatmentfailure.Therefore,findingawaytoreversedrugresistanceisanurgentissueinbreastcancertreatment.

Quercetin,anaturalflavonoidfoundinvariousplants,hasbeenshowntohaveanti-cancerproperties.StudieshaveshownthatquercetincanenhancethesensitivityofbreastcancercellstodoxorubicinbyinhibitingtheexpressionofP-gpandBCRP,whicharetwomajorresistance-relatedproteins.P-gpandBCRPcanpumpdrugsoutofcancercells,reducingtheconcentrationofintracellulardrugsandcausingdrugresistance.QuercetincaninhibittheexpressionofP-gpandBCRP,therebyincreasingtheconcentrationofdoxorubicinincancercellsandreducingdrugresistance.

Inaddition,theepithelial-mesenchymaltransition(EMT)processiscloselyrelatedtotumormalignancyanddrugresistance.EMTisaprocessinwhichepithelialcellstransformintomesenchymalcells,whichenhancestheinvasionandmigrationabilityofcancercellsandreducestheefficacyofchemotherapy.QuercetincanreversetheEMTprocessbyupregulatingtheexpressionofE-cadherin,anepithelialcellmarker,anddownregulatingtheexpressionofN-cadherinandvimentin,whicharemesenchymalcellmarkers.Thisindicatesthatquercetincannotonlyenhancethesensitivityofbreastcancercellstodoxorubicinbutalsoinhibitthemalignancyofbreastcancercells.

Inconclusion,quercetincanreversedrugresistanceinbreastcancertreatmentbyinhibitingtheexpressionofresistance-relatedproteinssuchasP-gpandBCRP,andbyreversingtheEMTprocess.Therefore,quercetinhasthepotentialtobecomeanewdrugtoreversedrugresistanceinbreastcancertreatment,providinganewstrategyforbreastcancertreatmentFurthermore,quercetinhasbeenshowntohaveanti-inflammatoryandantioxidantpropertieswhichcanalsoaidincancertreatment.Severalstudieshavereportedthatquercetincaninhibittheproliferationandmigrationofbreastcancercellsbyregulatingvarioussignalingpathways,suchasMAPK,PI3K/AKT,andNF-κB.ItalsoinducesapoptosisinbreastcancercellsbyactivatingcaspaseenzymesanddownregulatingtheexpressionofBcl-2,ananti-apoptoticprotein.

Inadditiontoitspotentialasachemosensitizer,quercetincanalsoactasachemopreventiveagentforbreastcancer.Quercetinhasbeenshowntoreducetheriskofbreastcancerbyinhibitingtheinitiation,progression,andmetastasisofbreastcancercells.Itcanalsomodulatethelevelsofestrogeninthebody,whichisknowntoinfluencetheriskandprogressionofbreastcancer.Moreover,quercetinpossessesanti-angiogenicproperties,whichcaninhibitthegrowthofbloodvesselsthatfeedcancercells,leadingtoareductionintumorgrowth.

Quercetinisanaturallyoccurringcompoundthatisavailableinmanydietarysourcessuchasfruits,vegetables,andnuts.Itisasafeandnon-toxiccompoundthatcanbeeasilyincorporatedintothedietofbreastcancerpatients.However,theefficacyandsafetyofquercetinasachemosensitizerandchemopreventiveagentshouldbevalidatedinclinicaltrialsbeforeitsroutineuseinbreastcancertreatment.

Inconclusion,quercetinholdssignificantpromiseasapotentchemosensitizerandchemopreventiveagentforbreastcancer.Itsabilitytoreversedrugresistance,inhibitproliferationandmigration,induceapoptosis,andmodulateestrogenlevelsmakesitapromisingcandidateforbreastcancertreatment.Furtherresearchisrequiredtounderstandthemechanismofactionofquercetinanditspotentialsideeffects,pavingthewayforitsroutineuseinbreastcancertreatmentMoreover,studieshavealsobeenconductedonthepotentialuseofquercetinforprostatecancertreatment.Ithasbeenshowntoinhibitproliferation,induceapoptosis,andsuppresstumorgrowthinvitroandinvivo.Quercetin'sabilitytomodulateimportantregulatoryproteinssuchasBcl-2,NF-kB,andAktmakesitanattractiveagentforprostatecancertreatment.

Inadditiontoitsanticancerproperties,quercetinhasalsobeenshowntohavebeneficialeffectsoncardiovascularhealth.Itsantioxidantandanti-inflammatoryeffectshavebeenlinkedtoareductioninoxidativestressandimprovedlipidandglucosemetabolism.Furthermore,quercetinhasbeenshowntoinhibitplateletaggregationandimproveendothelialfunction,highlightingitspotentialroleinpreventingcardiovasculardiseases.

QuercetinhasalsobeeninvestigatedforitspotentialinamelioratingneurodegenerativediseasessuchasAlzheimer'sandParkinson'sdisease.Itsabilitytoinhibitamyloidbetaaggregation,reduceoxidativestress,andactivateneuronalsignalingpathwayshasbeendemonstratedinanimalandinvitrostudies.Ithasalsobeenshowntoenhancecognitivefunctionandmemoryinanimalmodels.

However,despitethepromisingresultsofpreclinicalstudies,clinicaltrialsinvolvingquercetinhaveyieldedconflictingresults.Studiesinvestigatingtheuseofquercetinforallergy,asthma,andinflammationhavereportedpositiveresults,whiletrialsonitsuseforprostatecancerandcardiovasculardiseaseshaveyieldedmixedresults.Thishighlightstheneedforfurtherresearchtofullyunderstandthepotentialbenefitsandlimitationsofquercetinuse.

Inconclusion,quercetinisa