双氢青蒿素抑制胶质瘤细胞生长机制

目的 探讨双氢青蒿素对胶质瘤细胞C6生长影响及可能机制。方法 培养大鼠脑胶质瘤C6细胞,噻唑蓝法检测双氢青蒿素对C6细胞生长抑制率,annexin V/PI检测C6细胞凋亡率;ELISA法检测细胞培养液上清中cyclinD1、Bax和casepase-3蛋白表达变化;Western blot法检测Bax和Bcl-2蛋白表达量。结果 双氢青蒿素可明显抑制C6细胞生长,以作用48 h最为明显,0.05、0.50、5.00和50.00μmol/L双氢青蒿素组细胞生长抑制率分别为(83.96±1.08)% 、(74.04±3.54)% 、(68.70±9.20)% 和(57.25±7.01)%,与对照组(100.00±1.07)% 比较,差异有统计学意义(P<0.01);50.00μmol/L双氢青蒿素组细胞凋亡率[(25.98±3.95)%]明显高于对照组[(2.32±0.78)%],差异有统计学意义(P<0.01);与对照组比较,各剂量双氢青蒿素组C6细胞培养液上清中caspase-3分泌增加,50.00μmol/L双氢青蒿素组细胞Bax蛋白表达增加,Bcl-2蛋白表达减少,Bax/Bcl-2比值增加。结论 双氢青蒿素通过下调cyclin D1蛋白,上调Bax/Bcl-2比值使caspase-3蛋白活化,从而抑制胶质瘤细胞生长。

Inhibitive effect of dihydroartemisinin on proliferation of glioma cells and its mechanism

Objective To study inhibitive effect of dihydroartemisinin(DHA)on proliferation of glioma C6 cells and to explore the mechanism of the effect.Methods C6 cells were cultured;the viability of the cells was detected with 3-(4,5-dimethylthiazol-2-yl)-2,5 phenyltetrazolium bromide(MTT)assay;the apoptotic rate of the cells was determined with annexin V/propidium iodide(V/PI)assay;the secretions of cyclin D1,bax,and caspase-3 proteins were detected with enzyme-linked immunosorbent assay(ELISA);the expressions of Bax and Bcl-2 proteins were examined with Western blot.Results DHA could significantly inhibit the proliferation of glioma C6 cells and the inhibition was the most obvious at 48 hours of DHA treatment.The viabilities of glioma C6 cells treated with 0.05,0.50,5.00 and 50.00μmol/L DHA for 48 hours were 83.96±1.08%,74.04±3.54%,68.70±9.20%,and 57.25±7.01%,respectively,with signifi-cant decreases compared to that of the control group(100.00±1.07%)(all P<0.01).Compared with the control group,the glioma C6 cells treated with 50.00μmol/L DHA showed a significantly increased apoptotic rate(25.98±3.95% vs.2.32±0.78%,P<0.01)),decreased expressions of cyclin D1 and Bcl-2 protein,and increased expressions of Bax and caspase-3 protein and Bax/Bcl-2 ratio.Conclusion Dihydroartemisinin could inhibit the growth of glioma cells through down-regulating the expression of cyclin D1 protein and up-regulating the expression of Bax/bcl-2,and the activated expression of caspase-3 protein.