白藜芦醇调控TGF-β1/Smad信号通路对脑胶质瘤细胞增殖、凋亡的影响

Effects of resveratrol on proliferation and apoptosis of glioma cells by regulating TGF-β1/Smad signaling pathway

目的探究白藜芦醇调控转化生长因子-β1(TGF-β1)/Smad信号通路对脑胶质瘤细胞增殖、凋亡的影响。方法将人脑胶质瘤T98G细胞分为对照组、25μmol/L白藜芦醇组、50μmol/L白藜芦醇组、100μmol/L白藜芦醇组、5-氟尿嘧啶(5-FU)组、LY2109761(LY)组和SRI-011381(SRI)组,干预24 h。用活细胞计数、5-乙炔基-2'-脱氧尿嘧啶核苷、Hoechst 33258染色、黏附实验、Transwell小室及蛋白免疫印迹法分析细胞活力、增殖、凋亡、黏附、侵袭能力及细胞周期蛋白D1、半胱氨酸蛋白酶-3和TGF-β1/Smad信号通路相关蛋白表达水平。结果50、100μmol/L白藜芦醇组和5-FU组较对照组的细胞活力降低(P<0.05)。50μmol/L白藜芦醇组和5-FU组较对照组细胞增殖率、黏附、侵袭能力及细胞周期蛋白D1、TGF-β1、p-Smad3蛋白表达水平降低,而细胞凋亡、半胱氨酸蛋白酶-3和Smad7蛋白表达水平增强(P<0.05);LY组上述指标的变化进一步增强(P<0.05),而SRI组上述指标则与LY组的趋势相反(P<0.05)。结论白藜芦醇可抑制人脑胶质瘤T98G细胞的增殖、黏附、侵袭,并诱导其凋亡,其作用机制可能与抑制TGF-β1/Smad信号通路的活化有关。

Objective To investigate the effect of resveratrol on the proliferation and apoptosis of glioma cells by regulating transforming the growth factor-β1(TGF-β1)/Smad signaling pathway.Methods Human glioma T98G cells were divided into a control group,25μmol/L resveratrol group,50μmol/L resveratrol group,100μmol/L resveratrol group,5-fluorouracil(5-FU)group,LY2109761(LY)group and SRI-011381(SRI)group for 24 hours.Cell viability,proliferation rate,apoptosis,adhesion,invasion ability,expression of CyclinD1,Caspase-3 and TGF-β1/Smad signaling pathway and related protein expression levels were analyzed by cell count,5-ethynyl-2'deoxyuracil,Hoechst 33258 staining,adhesion assay,Transwell chamber and Western blotting.Results The cell viability of 50,100μmol/L resveratrol groups and the 5-FU group was lower than that of the control group(P<0.05).Compared with the control group,the cell proliferation rate,adhesion,invasion ability and protein levels of CyclinD1,TGF-β1 and p-Smad3 in the 50μmol/L resveratrol group and 5-FU group were decreased,while the apoptosis rate,Caspase-3 and Smad7 protein levels increased(P<0.05).The changes in the above indexes in the LY group were further strengthened(P<0.05),while those of the SRI group had an opposite trend to the LY group(P<0.05).Conclusion Resveratrol can inhibit the proliferation,adhesion and invasion of human glioma T98G cells and induce their apoptosis,whose mechanism may be connected to the inhibition of the activation of the TGF-β1/Smad signaling pathway.