沉默Bcl-XL逆转人胶质瘤获得性SLC22A18的耐药

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。

Overcoming acquired resistance by SLC22A18 silencing in human glioma

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.