沉默Bcl-XL逆转人胶质瘤获得性SLC22A18的耐药  

Overcoming acquired resistance by SLC22A18 silencing in human glioma

作　　者：杨标 楚胜华[1] 马延斌[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院神经外科,上海201999

出　　处：《现代肿瘤医学》2018年第7期981-984,共4页Journal of Modern Oncology

基　　金：教育部留学回国人员科研启动基金项目(编号:082003);上海市卫生和计划生育委员会科研基金面上项目(编号:201540266);上海交通大学医工交叉研究基金项目(编号:YG2015MS25);上海交通大学医学院附属第三人民医院自然科学研究基金项目(编号:syz2015-015)

摘　　要：目的:探讨RNA干扰Bcl-XL(siRNA)在人胶质瘤获得性SLC22A18的耐药中的作用。方法:以Bcl-XL siRNA转染获得性SLC22A18耐药的人胶质瘤U251-SLC22A18/R细胞,用重组人SLC22A18蛋白处理,MTT法和流式细胞仪检测肿瘤细胞的存活率,免疫印迹法检测凋亡相关蛋白Caspase-3和Caspase-8的表达情况。结果:Bcl-XL siRNA能够降低U251-SLC22A18/R细胞中Bcl-XL的表达,也能逆转其对SLC22A18的耐药。U251-SLC22A18/R细胞经过Bcl-XL siRNA和重组人SLC22A18蛋白共同处理4 h后细胞凋亡率>50%,细胞存活率<30%;而对照组和重组人SLC22A18蛋白处理组的细胞凋亡率和存活率无明显变化。经Bcl-XL siRNA与重组人SLC22A18蛋白联合处理后,U251-SLC22A18/R细胞中Caspase-3和Caspase-8均明显活化。结论:Bcl-XL siRNA能有效逆转人胶质瘤获得性SLC22A18的耐药,为治疗胶质瘤耐药提供一种新的思路。Objective：To study the reversing effect of Bcl-XL small interfering RNA （siRNA） on the acquired resistance to SLC22A18 in human glioma.Methods：Human glioma U251-SLC22A18/R cells,with acquired resistance to SLC22A18,were transfected with Bcl-XL siRNA followed by the treatment of SLC22A18 protein.The survival rate of U251-SLC22A18/R cells was respectively analyzed by MTT and FACS methods,and activation of apoptotic signaling proteins Caspase-3 and Caspase-8 was assessed by Western blotting analysis.Results：Bcl-XL siRNA could effectively decrease the protein expression of Bcl-XL and reversed the acquired resistance to SLC22A18 in U251-SLC22A18/R cells.After the combination treatment of Bcl-XL siRNA and SLC22A18 protein for 4 h,the cell apoptotic rate was more than 50% and the survival rate was less than 30%.There was no effect on the survival rate after the control treatment or SLC22A18 protein treatment alone.Caspase-3 and Caspase-8 were significantly activated after the the combination treatment with Bcl-XL siRNA and SLC22A18 protein.Conclusion：Bcl-XL siRNA can reverse the acquired resistance to SLC22A18 in human glioma,it might be a novel strategy for overcoming the resistance in glioma therapy.

关 键 词：胶质瘤 SLC22A18 耐药 BCL-XL RNA干扰 

分 类 号：R739.41[医药卫生—肿瘤]