紫杉醇协同肿瘤坏死因子相关凋亡诱导配体抑制胶质瘤细胞活性的探讨

Experimental research on biological activities of glioma cells inhibited by TRAIL in combination with paclitaxel

目的探讨紫杉醇(PX)联合肿瘤坏死因子相关凋亡诱导配体(TRAIL)对胶质瘤U251细胞凋亡作用的影响及其可能机制。方法分别采用改良MTT法和流式细胞术检测PX和TRAIL单独用药以及TRAIL/PX联合用药U251细胞后细胞增殖和凋亡的情况,采用Western bloting法检测PX对U251细胞TRAIL受体DR4和DR5表达的影响。结果 TRAIL和PX单独用药对U251细胞增殖均具有抑制作用且呈浓度依赖性,TRAIL/PX联合作用对U251细胞生长抑制率和凋亡率均大于单独用药(P<0.05),TRAIL/PX联合用药与单独用药相比可显著上调DR4表达(P<0.05),DR5表达无明显变化。结论 PX可协同TRAIL上调DR4的表达,进而提高胶质瘤细胞对TRAIL的敏感性,抑制细胞增殖和诱导细胞凋亡。

Objective To explore the effects of paclitaxel （PX）in combination with tumor necrosis factor-related apop-tosis-inducing ligand （TRAIL）on glioma U251 cell apoptosis and its possible mechanism.Methods The proliferation and apoptosis of U251 cells treated by TRAIL/PX in combination or alone at different concentrations were detected with modified MTT and flow cytometry.Proteins of U251 cell TRAIL death receptor DR4 and DR5 were measured with Western blot assay.Results Both TRAIL and PX had inhibitory effect on U251 cell proliferation in a concentration-dependent manner,combined TRAIL/PX treatment had remarkably higher inhibitory effect on cell growth and apoptosis of U251 cells than either drug used lone （P 〈0.05）.Furthermore,combined TRAIL/PX treatment showed a synergis-tic effect on U251 to upregulate the expression of DR4 （P 〈0.05）,but had no effect on the expression of DR5. Conclusions PX can improve the sensitivity of glioma U251 cells to TRAIL by upregulation of DR4,and then inhibit glioma cell proliferation and induce apoptosis.