白藜芦醇通过下调PRMT5表达抑制肝胆管癌SMMC-7721细胞的增殖、侵袭和细胞周期

Resveratrol inhibits proliferation,invasion and cell cycle of hepatobiliary carcinoma SMMC-7721 cells by downregulating the expression of PRMT5

目的:探究白藜芦醇(Res)通过调控PRMT5表达对肝胆管癌SMMC-7721细胞增殖、侵袭、细胞周期的影响及其机制。方法:常规培养正常肝细胞LO2和SMMC-7721细胞,用0、20、40、80μmol/L的Res进行处理,用qPCR法、MTT法、Transwell实验、流式细胞术和WB法分别检测Res处理后PRMT5 mRNA在LO2和SMMC-7721细胞中的表达,Res对SMMC-7721细胞增殖能力、侵袭能力、细胞周期和凋亡,以及PRMT5、cyclin D1和cyclin E1蛋白表达的影响。结果:PRMT5在SMMC-7721细胞中呈高表达(P<0.01);20、40、80μmol/L Res均能明显抑制PRMT5 mRNA和蛋白在SMMC-7721细胞中的表达(均P<0.01),抑制SMMC-7721细胞的增殖能力(P<0.01)和侵袭能力(P<0.05),阻滞SMMC-7721细胞周期于G0/G1期并促进其凋亡(P<0.01),明显抑制SMMC-7721细胞中周期蛋白cyclin D1、cyclin E1蛋白的表达(P<0.01)。结论:PRMT5在SMMC7721细胞中呈高表达,Res可有效抑制SMMC-7721细胞的增殖和侵袭能力并诱导其凋亡,其机制可能与抑制PRMT5表达相关。

Objective:To investigate the effects of resveratrol(Res)on the proliferation,invasion,and cell cycle of hepatobiliary carcinoma SMMC-7721 cells by regulating protein arginine methyltransferase 5(PRMT5)expression and its underlying mechanism.Methods:Normal hepatocytes LO2 and hepatobiliary carcinoma SMMC-7721 cells were routinely cultured and treated with 20,40,80μmol/L Res.qPCR assay was used to detect the mRNA expression of PRMT5 in LO2 cells,SMMC-7721 cells and Res-treated SMMC-7721 cells,respectively.The effects of Res on the proliferation,invasion,and cell cycle and apoptosis were examined using MTT assay,Transwell assay,and flow cytometry,respectively.WB assay was used to detect the protein expression of PRMT5,cyclin D1 and cyclin E1 in SMMC-7721 cells.Results:PRMT5 was highly expressed in SMMC-7721 cells(P<0.01).20,40,and 80μmol/L Res significantly inhibited the mRNA and protein expression of PRMT5 in SMMC-7721 cells(all P<0.01),suppressed the proliferation(P<0.01)and invasion(P<0.05)abilities of SMMC-7721 cells,and blocked SMMC-7721 cell cycle in G2/M phase as well as promoted its apoptosis(all P<0.01);Besides,Res significantly inhibited the protein expression levels of cyclin D1 and cyclin E1 in SMMC-7721 cells(all P<0.01).Conclusion:PRMT5 is highly expressed in SMMC7721 cells.Res can effectively inhibit the proliferation and invasion abilities of SMMC-7721 cells and induce cell apoptosis,and its possible mechanism is related to the inhibition of PRMT5 expression.