TRAIL联合美伐他汀增强对SWO-38细胞的抑瘤作用及其机制研究  

Synergistic antitumor activity of TRAIL combined with mevastatin in glioma SWO-38 cell line and its mechanism

作　　者：仲飞[1] 吴祥元[1] 杨静[2] 林曲[1] 董敏[1] 温景芸[1] 

机构地区：[1]中山大学附属第三医院肿瘤内科,广州510630 [2]中山大学附属第三医院特诊医学中心,广州510630

出　　处：《中华神经医学杂志》2009年第12期1207-1212,共6页Chinese Journal of Neuromedicine

基　　金：广东省科技计划项目（2006b36003017）

摘　　要：目的探讨肿瘤坏死因子相关细胞凋亡诱导配体（TRAIL）单独或联合美伐他汀对人胶质瘤细胞SWO-38增殖和凋亡的影响及其作用机制。方法人胶质瘤细胞SWO-38分别用人重组可溶性TRAIL蛋白（rsTRAIL）、美伐他汀及两者联用处理：MTT法检测细胞增殖情况：双染色流式细胞仪检测细胞凋亡情况；间接免疫荧光染色结合流式细胞技术检测细胞表面TRAILR，／DR4和TRAILR；DR5分子表达；RT-PCR方法检测TRAILR1／DR4和TRAILR2／DR5 mRNA表达。结果rsTRAIL和美伐他汀在单用或联用时均可抑制SWO-38细胞增殖，诱导其凋亡，并在一定范围内呈时间、剂量依赖性；联合用药组细胞增殖抑制率和凋亡率明显高于单用rsTRAIL或美伐他汀组，比较差异有统计学意义（P〈0．05）。美伐他汀单独或联合rsTRAIL作用于SWO-38细胞72h后，死亡受体TRAIL R1／DR4和TRAIL R2/DR5在细胞表面的表达明显较对照组细胞增强。其mRNA表达水平亦相应增加，比较差异均有统计学意义（P〈0．05）。结论rsTRAIL与美伐他汀联合使用可增强对人胶质瘤细胞SWO-38的增殖抑制和凋亡诱导效应，其机制可能是美伐他汀增加SWO-38细胞TRAIL R1／DR4和TRAIL R2/DR5 mRNA表达、上调细胞表面TRAIL死亡受体从而增加其对rsTRAIL的敏感性。Objective To investigate the effects of tumor necrosis-related apoptosis-inducing ligand （TRAIL）, mevastatin, or their combinations on the proliferation and apoptosis in glioma SWO-38 cells and their mechanisms. Methods The human glioma cell line SWO-38 was treated with human recombinant soluble TRAIL （rsTRAIL） and mevastatin, respectively, or their combinations. The proliferation of SWO-38 cells was analyzed with MTT assay; the cell apoptosis was detected by flow cytometry （Annexin V-FITC-PI assay）; the expressions of TRAIL R1/DR4 and TRAIL R2/DR5 on the cell surface were determined by indirect fluorescence staining and flow cytometry analysis; the mRNA expressions of TRAIL R1/DR4 and TRAIL R2/DR5 were detected by reverse transcription-polymerase chain reaction. Results The rsTRAIL and mevastatin, used alone or in combination, inhibited the cell proliferation of SWO-38 cells and induced their apoptosis in a time- and dose-dependent manner. The combination of rsTRAIL and mevastatin remarkably inhibited the proliferation and induced the apoptosis as compared with the rsTRAIL or mevastatin alone （P〈0.05）. Seventy-two hours after treatment, the expressions of TRAIL R1/DR4 and TRAIL R2/DR5 in the treatment groups were significantly higher as compared to those in the normal control group, and so was their mRNA expression level （P〈0.05）. Conclusion Both rsTRAIL and mevastatin can inhibit the proliferation and induce the apoptosis of SWO-38 cell; their combinations have a synergistic effect probably through the up-regulation of TRAIL R1/DR4 and TRAIL R2/DR5 expressions and their mRNA expressions on cell surface.

关 键 词：肿瘤坏死因子相关细胞凋亡诱导配体 美伐他汀 神经胶质瘤 细胞增殖 细胞凋亡 

分 类 号：R686[医药卫生—骨科学]