【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。更多还原

【Abstract】 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.更多还原