摘要
Abstract
Objective:To investigate the inhibitory effect of Empagliflozin on human renal clear cell adenocarcinoma cells and its related mechanisms.Methods:Bioinformatics analysis was used to screen differential genes and pathways.In vitro experiments were conducted using 786-O cells,which were divided into a control group and an Empagliflozin group(combined with the AMPK inhibitor BAY-3827 or agonist Nilotinib).Western blotting and qPCR were used to detect the expression of AMPK,PTEN,HDAC11,YAP,BRD4 proteins and epithelial-mesenchymal transition(EMT)markers.Scratch and Transwell assays were performed to evaluate cell migration and invasion capabilities.A nude mouse tumorigenesis experiment was conducted to validate the regulatory role of the AMPK pathway.Results:Bioinformatics analysis screened 1384 differentially expressed genes(800 up-regulated,584 down-regulated),enriched in PI3K-Akt,chemokines and Rap1 pathway;Engleretin significantly up-regulated p-AMPK,PTEN,HDAC11,while inhibiting YAP/BRD4 nuclear expression;down-regulated Snail,Slug mRNA,and enhanced E-cadherin mRNA expression;Emgleretin reduced cell migration and invasion,which were reversed by BAY-3827 but further inhibited by Nilotinib.In vivo studies showed Empagliflozin suppressed tumor growth,with AMPK-KD mice exhibiting larger tumor and AMPK-OE mice smaller tumors.Conclusion:Empagliflozin inhibits the progression of renal clear cell adenocarcinoma by activating the AMPK/PTEN/HDAC11 pathway,suppressing YAP/BRD4 nuclear localization and the EMT process,providing new mechanistic insights for clinical treatment.关键词
恩格列净/Yes相关蛋白/单磷酸腺苷激活的蛋白激酶/上皮间质转化/肾透明细胞腺癌Key words
Empagliflozin/Yes associated protein/adenosine monophosphate-activated protein kinase/epithelial-mesenchymal transition/clear cell renal cell adenocarcinoma分类
医药卫生
