抑制JNK通路对TRAIL诱导胃癌细胞凋亡影响的研究  

Effect of JNK signaling pathway inhibition on TRAIL-induced apoptosis in human gastric cancer cells

作　　者：刘静[1] 曲秀娟[1] 刘云鹏[1] 徐玲[1] 侯科佐[1] 张晔[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001

出　　处：《中华肿瘤防治杂志》2011年第7期481-484,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(30770993)

摘　　要：目的:研究JNK信号传导通路对TRAIL诱导胃癌细胞凋亡的影响。方法:四甲基偶氮唑蓝(MTT)比色法测定细胞活力;蛋白质印迹法检测细胞内磷酸化JNK及总JNK的表达水平;流式细胞术碘化丙啶(PI)染色检测细胞凋亡及细胞周期分布。为研究JNK通路活性对TRAIL抗肿瘤作用的影响,将实验分为空白对照组、TRAIL单药组(100μg/L)、JNK抑制剂组(SP600125,20μmol/L)和联合用药组(SP600125+TRAIL)。结果:采用25、50、100和200μg/LTRAIL作用于MGC803细胞24 h,细胞活力仅轻度下降。进一步研究发现,TRAIL作用后细胞内磷酸化JNK水平明显升高,提示JNK信号通路被活化。同TRAIL单药组相比,联合用药组的细胞活力明显降低〔(53.5±3.2)%vs(88.3±1.1)%,P<0.05〕,细胞凋亡明显增加〔(21.3±5.1)%vs(5.7±0.1)%,P<0.05〕,G2/M期细胞比例明显升高〔(38.0±6.0)%vs(25.7±2.9)%,P<0.05〕。结论:抑制JNK通路能明显增强TRAIL对MGC803细胞的抗肿瘤作用,其机制可能与诱导细胞凋亡及G2/M期阻滞有关。OBJECTIVE： To investigate the effect of JNK signaling pathway on TRAIl. induced apoptosis in human gastric cancer cells. METHODS： Methyl thiazolyl tetrazolium （MTT） assay was used to determine the cell viability; Western blotting was used to detect the levels of phosphor-JNK and total JNK; Flow cytometry following Propidium Iodide （PI） staining was used to determine the apoptosis as well as cell cycle distribution. The trial included： the control group, TRAIL group （100 μg/L）, JNK inhibitor group （SP600125,20 μmol/L）, and the combined group （SP600125 ＋ TRAIL）. RESULTS： Under the treatment of 25, 50, 100 and 200 μg/I. TRAIL for 24 h,the viability of MGC803 cells was slightly affected. Further study showed that the level oI phosphor JNK was up regulated obvi ously under the treatment of TRAIL, which indicated the activa- tion of JNK signaling pathway. Compared with TRAIL group, the cell viability of the combined group was reduced （（53. 5 ± 3.2）% vs （88. 3±1. 1）%,P〈20. 05）, the apoptosis was enhanced（（21.3±5. 1） % vs （5. 7±0. 1）%, P〈0.05）, and the ceils arrested at G/M phase increased （38. 0± 6. 0）% vs （25.7 ± 2.9） %, P〈0.05） significantly. CONCLUSION： Inhibition of JNK activity enhances significantly the anti-tumor effect of TRAIl. on MGC803 cells, and the mechanism may involve the induction of apoptosis and arresting of cell cycle at G2/M phase.

关 键 词：胃肿瘤 JNK TRAIL 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]