表阿霉素提高胃癌BGC823细胞对TRAIL的敏感性  

Epirubicin increases the sensitivity of gastric cancer BGC823 cells to TRAIL

作　　者：徐玲[1] 曲秀娟[1] 刘云鹏[1] 刘静[1] 罗颖[1] 张晔[1] 侯科佐[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：《现代肿瘤医学》2012年第3期496-499,共4页Journal of Modern Oncology

基　　金：高等学校博士学科点专项科研基金(No.20102104120008);中国医科大学附属第一医院科学研究基金(No.fsfh1003)

摘　　要：目的:研究表阿霉素对TRAIL诱导胃癌细胞BGC823细胞凋亡的影响,探讨脂筏和死亡受体4(DR4)在TRAIL诱导细胞凋亡中的作用。方法:采用MTT法测定细胞活力,流式细胞仪检测细胞凋亡,免疫荧光显微技术检测脂筏和DR4在细胞膜的分布。结果:(0.1-50)μg/ml表阿霉素处理BGC823细胞24h,抑制细胞增殖50%的药物浓度(IC50)为(4.61±0.62)μg/ml。在BGC823细胞中,100ng/ml的TRAIL导致轻度的增殖抑制和细胞凋亡,TRAIL(100ng/ml)联合表阿霉素(4.61μg/ml)引起明显的增殖抑制和细胞凋亡(P<0.05)。与对照组相比,100ng/ml的TRAIL作用BGC823细胞24 h,没有引起明显的脂筏聚集或DR4聚集。表阿霉素(4.61μg/ml)明显促进脂筏聚集和DR4聚集,同时观察到DR4和脂筏的共定位。表阿霉素和TRAIL联合作用24 h,同样观察到DR4定位在聚集的脂筏内。结论:表阿霉素通过促进DR4在脂筏聚集增强TRAIL诱导的胃癌BGC823细胞凋亡。Objective：To assess the effect of epirubicin on TRAIL-induced apoptosis in gastric cancer BGC823 cells,and the action of lipid rafts and death receptor 4（DR4） in TRAIL-induced apoptosis.Methods：Cell proliferation was measured using MTT assay.Cell apoptosis was determined by flow cytometry.The distribution of lipid raft and DR4 in cell membranes was analyzed by immunofluorescence microscopy.Results：BGC823 cells were treated with（0.1-50）μg/ ml epirubicin for 24 h,the concentration of 50% inhibition of cell proliferation（IC50） was（4.61±0.62）μg/ml.Treatment with 100 ng/ml TRAIL for 24 h resulted in a slight reduction in cell viability and a little increase in cell apoptosis in BGC823 cells.Treatment with TRAIL（100ng/ml） and epirubicin（4.61μg/ml） leaded to a significant reduction in cell viability and a dramatic increase in cell apoptosis（P0.05）.100ng/ml TRAIL did not induce obvious lipid raft aggregation or DR4 clustering.Epirubicin（4.61μg/ml） significantly promoted lipid rafts and DR4 aggregation,and the colocalization of DR4 and lipid rafts.Treatment with epirubicin and TRAIL for 24 h also induced DR4 clustering in aggregated lipid rafts.Conclusion：Epirubicin enhanced TRAIL-induced apoptosis in gastric cancer BGC823 cells by clustering DR4 into lipid rafts.

关 键 词：TRAIL 表阿霉素 胃癌 脂筏 死亡受体 

分 类 号：R735.2[医药卫生—肿瘤]