槲皮素通过调控Hippo通路蛋白YAP表达抑制胃癌细胞增殖与迁移并促进其凋亡

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Abstract：ObjectiveToexplorethemolecular mechanismsbywhichquercetinregulatesproliferation，migrationand apoptosisofgastriccancercels.MethodsBioinformaticsanalysiswasconductedtoexaminethediferentialexpresionof Hippopathaproteinyes-assiatedprotein（YAP）betweengastriccancerandnormaltissuesanditscorrelationwithpatient survivalrates.CCK-8assaywasusedtoevaluate theeffectofquercetinonviabilityof gastriccancer HGC-27cels.The expression levels of YAPand phosphorylated YAP（p-YAP）in gastriccancerandnormal gastric tisues weredetected using Westernblotting.IC-27cellswitAockdotectsofuercetintreatmentoncellproliferation，igatioand apoptosisdaselldoto was determined using immunofluorescence staining.Rescue experiments were performed by overexpressing YAP in HGC-27 cels.ResultsAexprssionwasmakedlyloweingastricancetissstaninnoaltissesnditsexpressonlelwas negativelycorelatedwithpatientsurvivalates.QuercetinsignificantlyinibitedthesurvivalofHGC-27cells，promoted MST1andLAexpreionndcatedteHippoigalingpthayldingtoosporylai-medatediiaiof YAP，therebyreducingitsnucleartranslocation.BothYAPknockdownandquercetintreatmentsignificantlysuppressed proliferationandmigrationandpromotedapoptosisofHGC-27cels.OverexpressionofYAPsubstantiallyatenuatedthe inhibitoryefectsofquercetininHGC-27cels.ConclusionQuercetininhibitsproliferationandmigrationandpromotes apoptosis of gastric cancer cells by promoting phosphorylation-mediated inactivation of YAP.

Keywords： Quercetin; Hippo signaling pathway; yes-associated protein; phosphorylation; gastric cancer

胃癌是目前世界范围内极为常见的致死癌症之一，据统计，全球目前的胃癌病例数已达97万例，居癌症发病率第5位，其中死亡约66万例，占全球癌症死亡例数的 6.8% ，是世界第5大癌症死亡率，同时也是中国的第3大癌症死亡率[2]。（剩余13024字）