组蛋白去乙酰化酶抑制剂曲古抑菌素通过上调Slug促进结直肠癌细胞上皮-间质转化的研究

摘要

Objective To investigate the molecular mechanism of Histone deacetylase inhibitor TSA-mediated epithelial-mesenchymal transition in colorectal cancer cell HCT116.Methods The migration capability of HCT116 cells treated by TSA was measured by wound healing test and morphological changes were observed.Western blot and quantitative real-time PCR detected the expressions of E-cadherin,Vimentin and Slug.Results TSA induced EMT transition and enhanced migration of HCT116 cells.TSA increased expressions of Slug in mRNA and protein levels.Moreover,knockdown Slug expression by si-RNA suppressed TSA-induced EMT in HCT116 cells.Conclusions Histone deacetylase inhibitor TSA induces EMT in HCT116 cells by up-regulation the expression of Slug.%目的 研究组蛋白去乙酰化酶抑制剂曲古抑菌素(TSA)诱导结直肠癌细胞HCT116发生上皮-间质转化(EMT)的潜在分子机制.方法 TSA处理结直肠癌细胞HCT116,观察细胞形态变化;划痕实验观察细胞迁移侵袭能力的变化.实时定量PCR、Western blot检测HCT116细胞EMT标志物以及Slug的表达情况.siRNA敲除Slug表达,Western blot检测HCT116细胞EMT标志物表达变化,以及细胞形态变化.结果 TSA可以促进结直肠癌细胞HCT116的迁移能力,诱导HCT116细胞发生EMT转化,包括细胞形态改变,EMT标志物表达变化.TSA可以促进EMT关键转录因子Slug的表达,包括蛋白和mRNA水平;敲除Slug表达可以抑制TSA诱导的EMT转化过程.结论 组蛋白去乙酰化酶抑制剂TSA通过上调Slug的表达促进结直肠癌细胞HCT116发生EMT转化,从而提高其迁移能力.