双硫仑通过调控ALDH-1抑制非小细胞肺癌A549细胞上皮间质转化的机制  

The Effect of Dithiulam on TGF-β_(1)-induced Epithelial-mesenchymal Transition in A549 cells by Regulating ALDH-1

作　　者：周志峰[1] 王少明[1] 阮君山[1] 许云禄[2] ZHOU Zhi-feng;WANG Shao-ming;RUAN Jun-shan;XU Yun-lu(Department of Pharmacy,Fujian Provincial Hospital,Fuzhou 350001,China;Department of Pharmacology,Fujian Medical University,Fuzhou 350121,China)

机构地区：[1]福建省立医院药学部,福建福州350001 [2]福建医科大学药理实验室,福建福州350001

出　　处：《海峡药学》2021年第11期7-10,共4页Strait Pharmaceutical Journal

基　　金：福建省自然科学基金资助(2018J01254);福建省自然科学基金资助(2020J011094);福建省立医院“创双高”火石(科研培育)基金项目资助(项目编号:2019-07)。

摘　　要：目的探索双硫仑(Disulfiram,DSF)通过调控ALDH-1(乙醛脱氢酶-1)对TGF-β_(1)诱导非小细胞肺癌细胞(Non-small cell lung cancer,NSCLC)上皮间质转化(epithelial-mesenchymal transition,EMT)的影响。方法通过TGF-β_(1)诱导A549细胞构建EMT模型。MTT实验检测DSF对TGF-β_(1)诱导NSCLC增殖的影响。Western blot分析双硫仑对EMT模型中ALDH-1、Vementin、E-cadherin蛋白表达水平的影响;结果TGF-β_(1)能有效诱导A549细胞发生EMT,由上皮样转化为间质化形态,而DSF能够逆转TGF-β_(1)诱导的形态变化。DSF对发生EMT的A549细胞增殖有抑制作用,IC_(50)为80μM。DSF显著降低Vementin和ALDH-1的表达,促进E-cadherin的表达。结论DSF通过调控ALDH-1能够逆转TGF-β_(1)诱导的A549细胞的EMT过程,从而抑制细胞的侵袭和迁移。OBJECTIVE To explore the effect of dithiulam(DSF)on TGF-β_(1)-induced epithelial-mesenchymal transition(EMT)by regulating ALDH-1(aldehyde dehydrogenase-1).METHODS A549 cells were induced by TGF-β_(1)to construct EMT model.MTT assay was used to detect the effect of DSF on TGF-β_(1)-induced proliferation of NSCLC.Western blot was used to analyze the effects of disulfiram on the protein expression levels of ALDH-1,Vementin and E-cadherin in EMT model.RESULTS TGF-β_(1)could effectively induce EMT in A549 cells from epithelioid to mesenchymal,while DSF could reverse the TGF-β_(1)-induced morphologic changes.DSF inhibited the proliferation of A549 cells with EMT(IC_(50)=80μM).DSF significantly decreased the expression of Vementin and ALDH-1,and promoted the expression of E-cadherin.CONCLUSION By regulating ALDH-1,DSF can reverse TGF-β_(1)-induced EMT process in A549 cells,thereby inhibiting cell invasion and migration.

关 键 词：双硫仑 上皮间质转化 ALDH-1 非小细胞肺癌 转化细胞生长因子β_(1) 

分 类 号：R965[医药卫生—药理学]