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塞来昔布下调sirtuin 1表达抑制转化生长因子-β1诱导人胃癌细胞SGC-7901上皮细胞-间充质转化过程的研究
Inhibition of SGC-7901 Epithelial-mesenchymal Transition Process Induced by TGF-β1 in Human Gastric Cancer Cells by Celecoxib via Down-regulating the Expression of Sirtuin 1
【摘要】 目的:探究塞来昔布(CXB)对转化生长因子-β1(TGF-β1)诱导人胃癌细胞SGC-7901上皮细胞-间充质转化(EMT)过程的影响及其分子机制。方法:用10 ng·ml-1TGF-β1诱导SGC-7901细胞建立EMT模型,将建模成功的胃癌细胞分为5组:模型组、白藜芦醇组(Res,50μmol·L-1)、CXB低(40μmol·L-1)、高(100μmol·L-1)剂量组、Res+CXB组(50μmol·L-1+100μmol·L-1),以未建模的SGC-7901细胞作为对照组,采用实时荧光定量PCR(qRT-PCR)检测SGC-7901中sirtuin 1 mRNA表达情况,分别采用MTT实验、划痕实验和transwell小室检测SGC-7901细胞增殖、迁移和侵袭情况,蛋白免疫印迹(Western Blot)检测SGC-7901细胞中钙粘附蛋白-E(E-cadherin)、波形蛋白(vimentin)表达情况。结果:模型组SGC-7901细胞呈现梭形和纺锤形,且细胞间隙变大、排列松散,提示造模成功。模型组和Res组SGC-7901细胞中sirtuin 1 mRNA表达水平、SGC-7901细胞增殖率、迁移能力、侵袭能力及vimentin表达水平显著高于对照组,E-cadherin表达水平显著低于对照组(P<0.05);与模型组相比,CXB低、高剂量组SGC-7901细胞中sirtuin 1 mRNA表达水平、SGC-7901细胞增殖率、迁移能力、侵袭能力及vimentin表达水平显著降低,E-cadherin表达水平显著升高(P<0.05);Res+CXB组SGC-7901细胞中sirtuin 1 mRNA表达水平、SGC-7901细胞增殖率、迁移能力、侵袭能力vimentin表达水平显著低于Res组,E-cadherin表达水平显著高于Res组(P<0.05)。结论:CXB能够下调SGC-7901细胞中sirtuin 1表达,进而抑制TGF-β1诱导的人胃癌细胞SGC-7901 EMT过程。
【Abstract】 Objective:To investigate the effect of celecoxib(CXB)on SGC-7901 epithelial-mesenchymal transition(EMT)process induced by TGF-β1 in human gastric cancer cells and its molecular mechanism.Methods:SGC-7901 cells were induced by 10ng·ml-1TGF-β1 to establish EMT model,and the gastric cancer cells were divided into five groups,named the model group,resveratol group(Res,50μmol·L-1),CXB low dose(40μmol·L-1)group,CXB high dose(100μmol·L-1)group,Res+CXB group(50μmol·L-1+100μmol·L-1),and the SGC-7901 cells without modeling were used as the control group.Real-time quantitative PCR(qRT-PCR)was used to detect SGC-7901 sirtuin 1 mRNA,and the cell proliferation,migration and invasion was detected by MTT assay,scratch assay and Transwell assay,respectively,the expressions of vimentin and E-cadherin were detected by Western blot.Results:The SGC-7901 cells in the model group showed shuttle and spindle shapes,the intercellular space became larger,and the cells became loosely arranged,which indicated that the modeling was successful.The expression level of sirtuin 1 mRNA,the proliferation,migration,invasion and vimentin expression of SGC-7901 cells in the model group and Res group were significantly higher than those in the control group,and the expression level of E-cadherin in SGC-7901 cells was significantly lower than that in the control group(P<0.05).Compared with those in the model group,the expression level of sirtuin 1 mRNA,the proliferation,migration,invasion and vimentin expression of SGC-7901 cells was significantly decreased,and the expression level of E-cadherin in SGC-7901 cells was significantly increased(P<0.05).The expression level of sirtuin 1 mRNA,the proliferation,migration,invasion and vimentin expression of SGC-7901 cells in Res+CXB group were significantly lower than those in Res group,and the expression level of E-cadherin was significantly higher than that in Res group(P<0.05).Conclusion:CXB can down-regulate SGC-7901 cells sirtuin 1 expression,and inhibit SGC-7901 EMT process induced by TGF-β1 in human gastric cancer cell.
【Key words】 Celecoxib; Gastric cancer; Histone deacetylase; Epithelial mesenchymal transition; E-cadherin; Vimentin;
- 【文献出处】 中国药师 ,China Pharmacist , 编辑部邮箱 ,2019年06期
- 【分类号】R96
- 【被引频次】8
- 【下载频次】118