氯喹增敏地塞米松或辐射对多发性骨髓瘤细胞的杀伤作用  

Sensitized cytotoxic effects of dexamethasone or radiation on multiple myeloma cells by chloroquine

作　　者：付慧[1] 陶玉龙[2] 倪敏[3] 李冬洁[3] 沈甫明[1,3] 

机构地区：[1]第二军医大学药学院药理学教研室,上海200433 [2]第二军医大学附属长征医院药学部,上海200003 [3]同济大学附属上海第十人民医院药学部,上海200072

出　　处：《药学实践杂志》2016年第3期210-214,共5页Journal of Pharmaceutical Practice

基　　金：国家重大新药创制(2011ZXJ09201-012)

摘　　要：目的 研究氯喹（chloroquine,CQ）,及CQ是否增敏化疗药物地塞米松（dexamethasone,DEX）或辐射对多发性骨髓瘤细胞株U266细胞的杀伤作用,并探讨其可能机制。方法 用细胞活性检测试剂盒（cell counting kit-8,cck8）检测CQ单药,以及CQ联用DEX对U266细胞增殖的影响,运用中效原理软件评估两药相互作用;cck8及流式细胞术分别检测CQ处理条件下辐射对U266细胞增殖和凋亡作用的改变;Western blot检测CQ合用DEX,以及CQ联合辐射对U266细胞内B细胞淋巴瘤-2（B-cellymphoma-2,Bcl-2）蛋白表达变化。结果 CQ及DEX对U266细胞的增殖抑制作用呈浓度依赖性,且CQ（3.9μmol/L）能够增强DEX（125μmol/L）对U266细胞的杀伤作用,并增加DEX降低细胞内抗凋亡蛋白Bcl-2的表达水平;不同辐射剂量（5～25 Gy）对U266细胞的生长抑制作用并无差异;CQ（1.0μmol/L）可以增加辐射对U266细胞的敏感性,诱导细胞凋亡。结论 CQ能够增敏DEX或辐射对U266细胞的杀伤作用,CQ增敏DEX的作用机制可能与抑制Bcl-2蛋白表达相关。Objective To investigate the role and possible mechanism of combination use of cbloroquine （CQ） with either dexamethasone （DEX） or radiation on multiple myeloma （MM） cell line U766. Methods cell viability of U266 treated with CQ alone, or CQ combined with either DEX or radiation was measured by cell counting kit-8 （cck8）. CalcuSyn method was used to assess effect of drugs interaction. Cell viability and apoptosis of U266 pre treated with CQ were also measured by cck8 and flow cytometry after radiation. Expression of B-cellymphoma-2 （Bcl-2） in U266 cells treated by CQ combined with DEX or radiation was determined by Western blot analysis. Results Either CQ or DEX displayed a dose dependent cell proliferalion in hibitory effect on U266 cells. Cytotoxic effect of DEX （125 μmol/L） on U266 cells was enhanced and expression of Bcl-2 pro- tein in U266 cells was decreased by combining with CQ （3.9μmol/L）. U266 cells were sensitized to radiation and cell death was induced by CQ （1.0μmol/L）. Conclusion CQ could sensitize cytotoxic effect of DEX or radiation on U266 cells, and the former was possibly related to down-regulation of Bcl 2 protein.

关 键 词：氯喹 地塞米松 辐射 多发性骨髓瘤细胞株U266细胞 增敏 

分 类 号：R96[医药卫生—药理学] R979.1[医药卫生—药学]