成纤维细胞激活蛋白对胃癌细胞增殖、迁移、侵袭的影响及机制研究  

Effect of Fibroblast Activation Protein on the Progression of Gastric Cancer

作　　者：杨肖军[1] 彭春伟[1] 黄超群[1] 程伏林[1] 熊斌[1] 李雁[1,2] 

机构地区：[1]武汉大学中南医院肿瘤科/湖北省肿瘤医学临床研究中心,湖北武汉430071 [2]北京世纪坛医院腹膜肿瘤科,北京100038

出　　处：《武汉大学学报（医学版）》2016年第6期900-904,共5页Medical Journal of Wuhan University

基　　金：2012年高等学校博士学科点专项科研基金(新教师类)(编号:20120141120057)

摘　　要：目的:探讨成纤维细胞激活蛋白(FAP)在胃癌细胞增殖、侵袭和迁徙过程中的作用及机制。方法:体外培养的人胃癌细胞株MGC803,分别加入不同浓度的FAP(50,100和150pmol/L)处理细胞48h;采用MTT法检测细胞增殖;细胞划痕实验检测FAP对MGC803迁徙能力的影响;Transwell侵袭实验检测FAP对MGC803侵袭能力的影响;RT-PCR、Western Blot检测细胞上皮间质转化(EMT)相关标志分子(Vimentin、E-cadherin、ZO-1、Ncadherin)及EMT的上游不同信号通路分子表达。结果:不同浓度的FAP可呈剂量依赖性促进胃癌细胞增殖、迁移及侵袭(P<0.05);RT-PCR、Western Blot检测结果显示FAP作用于MGC803细胞后诱导细胞上皮标志分子Ecadherin、ZO-1表达下调,间质标志分子Vimentin、N-cadherin表达上调,且均呈剂量依赖性(P<0.05);Western Blot检测上游不同信号通路分子表达结果显示,Wnt/β-catenin信号通路分子(DKK1、LEF-1)表达呈剂量依赖性上调,差异具有统计学意义(P<0.05)。结论:FAP可通过激活Wnt/β-catenin信号通路,调控活化EMT,促进胃癌细胞的增殖、迁徙和侵袭。Objective：To investigate the effect of fibroblast activation protein（FAP）on gastric cancer cell proliferation,invasion and migration process and its mechanisms.Methods：MGC803cells were exposed to different concentrations of FAP（50,100,and 150pmol/L）for 48h;cell proliferation was measured by MTT assay;Cell ability to migrate was measured by wound migration assay,and cell invasion was detected by Transwell invasion assay;RT-PCR and Western blot were adopted to study FAP effects on E-cadherin,N-cadherin,ZO-1,Vimentin and several signaling factors associated with epithelial mesenchymal transition（EMT）.Results：Different concentrations of FAP could promote gastric cancer cells proliferation,migration and invasion in a dose-dependent manner（P〈0.05）.The level of the epithelial markers E-cadherin and ZO-1were decreased,and the level of mesenchymal markers Vimentin and N-cadherin were increased in a dosedependent manner（P〈0.05）;Western Blot on the different upstream signaling pathways of EMT showed that Wnt/β-catenin signaling pathway molecules（DKK1,LEF-1）expression were increased in a dose-dependent manner（P〈0.05）.Conclusion：FAP can activate EMT and enhance gastric cancer cell proliferation,migration and invasion by activating Wnt/β-catenin signaling pathway.

关 键 词：成纤维细胞激活蛋白 MGC803 肿瘤侵袭 上皮间质转化 WNT/Β-CATENIN 

分 类 号：R730.5[医药卫生—肿瘤]