STAT3加重TGF-β1诱导的肝癌细胞上皮-间质转化的发生  

STAT3 aggravates TGF-β1 induced epithelial-to-mesenchymal transition in hepatocellular carcinoma cells

作　　者：刘婷[1] 吴俊成[1] 陆伦根[1] 徐铭益[1] 

机构地区：[1]上海交通大学附属第一人民医院消化科,200080

出　　处：《肝脏》2018年第2期128-132,共5页Chinese Hepatology

基　　金：国家自然基金面上项目(81570547);国家科技部十二五项目(2012ZX10002007-001-040;2013ZX10002004-002-003);院优秀青年培养计划(061405)

摘　　要：目的探讨IL-6/JAK/STAT3和Smad3/TGF-β1信号通路在肝癌细胞上皮-间质转化(EMT)发生过程中的作用。方法分别予TGF-β1、IL-6、AG490刺激人肝癌细胞株(HepG2、Bel7402、MHCC97H、HCCLM3)后,qPCR检测Snail、STAT3的mRNA表达水平,蛋白质免疫检测p-STAT3/STAT3、p-Smad3/Smad3、TGF-β1以及EMT相关分子标志物Snail、E-Cadherin、Vimentin的蛋白表达水平。结果 TGF-β1可以诱导HepG2细胞EMT的发生,下调E-Cadherin的表达,上调Vimentin、Snai的表达。IL-6在肝癌细胞中通过刺激STAT3,激活Smad3/TGF-β1通路,进而上调EMT相关分子标志物Snail、Vimentin的表达。AG490(一种JAK2的特异性抑制剂)抑制p-STAT3/STAT3、p-Smad3及EMT相关分子标志物Snail的表达。结论STAT3在TGF-β1诱导的肝癌细胞EMT发生过程中作为一个正向调控因子,IL6/JAK/STAT3和Snail/Smad3/TGF-β1信号通路协同促进肝癌细胞EMT的发生。Objective To investigate the underlying molecular mechanisms of interleukin-6/Janus kinase/signal transducer and activator of transcription(IL-6/JAK/STAT3)and Smad3/transforming growth factor-β1(Smad3/TGF-β1)signaling pathways during the epithelial to mesenchymal transition(EMT)process in hepatocellular carcinoma(HCC)cells.Methods Human HCC cell lines HepG2 and HCCLM3 were treated with TGF-β1,AG490 and IL-6,respectively.mRNA expressions of STAT3 and Snail were measured using quantitative PCR.Expressions of p-STAT3/STAT3,p-Smad3/Smad3,TGF-β1 and EMT-related markers were measured using western blotting.Results TGF-β1 induced EMT in HepG2 cells,dampen E-Cadherin expression and up-regulate expressions of vimentin,Snail,p-Smad2/3 and p-STAT3/STAT3.IL-6 activated Smad3/TGF-β1 pathway by stimulating STAT3 in human HCC lines,and up-regulated expressions of EMT-related molecular markers(Snail and Vimentin).AG490,the JAK2-specific inhibitor,inhibited expressions of pSTAT3/STAT3,p-Smad3 and Snail.Conclusion STAT3 aggravated TGF-β1-induced EMT and HCC metastasis,which performed a synergistical effect with IL-6/JAK/STAT3 and Snail/Smad3/TGF-β1 signaling pathways.

关 键 词：肝细胞癌 上皮-间质转化 信号转导和转录活化蛋白3 转化生长因子-Β1 

分 类 号：R735.7[医药卫生—肿瘤]