淫羊藿素对人多发性骨髓瘤耐药细胞株KM3/BTZ多药耐药性的逆转作用  

Icaritin Reverses Multidrug Resistance of Multiple Myeloma Cell Line KM3/BTZ

作　　者：李志远 李振杰 陈旭 黄幸儒 方梓青 张建国 方坚 

机构地区：[1]广州市正骨医院骨科,广东广州510045 [2]广州市荔湾区骨伤科医院骨关节科,广东广州510140 [3]广州中医药大学第三临床医学院关节科,广东广州510000 [4]广州中医药大学第三附属医院关节科,广东广州510240

出　　处：《中国实验血液学杂志》2017年第6期1690-1695,共6页Journal of Experimental Hematology

基　　金：广东省科技计划项目(2014A020212272);广东省中医药局(重点项目)(20164009)

摘　　要：目的:探讨淫羊藿素对人多发性骨髓瘤耐药细胞株KM3/BTZ多药耐药性的逆转作用及其可能的机制。方法:采用硼替佐米(bortezomib,BTZ)梯度诱导建立KM3/BTZ细胞株,MTT法检测KM3和KM3/BTZ对7种化疗药物的耐药性以及淫羊藿素对KM3/BTZ细胞的增殖抑制作用和耐药逆转作用,流式细胞术检测细胞凋亡,Western blot法检测Par-4、HSP27和P-gp蛋白表达变化。结果:KM3/BTZ对BTZ和其他6种化疗药物都产生耐药性,其中对BTZ的耐药指数(RI)最高,为17.84。淫羊藿素抑制KM3/BTZ细胞增殖并诱导其凋亡,使半致死浓度(IC50)由0.354μg/ml下调到0.149μg/ml,耐药逆转倍数为2.38倍;Par-4表达上调,HSP27和P-gp表达下调。结论:淫羊藿素能有效抑制KM3/BTZ细胞增殖,诱导其凋亡,具有逆转KM3/BTZ细胞多药耐药的作用,其作用机制可能与下调HSP27和P-gp,以及上调Par-4表达有关。Objective： To investigate the reversing effect of icaritin on multidrug resistance of multiple myeloma cell lines KM3/BTZ and its underlying mechanism. Methods： KM3/BTZ cells were established by a gradually ascending gradient induction of bortezomib（ BTZ）. The sensitivities of KM3 and KM3/BTZ cells to 7 chemotherapeutic drugs,the inhibition and reversal effects of icaritin on proliferation and drug-resistance of KM3/BTZ cells were analyzed by MTT.The apoptosis was analyzed by flow cytometry,and the expression of Par-4,HSP27 and P-gp were detected by Western blot. Results： KM3/BTZ cells were not only resistant to BTZ,but also to other 6 chemotherapeutic drugs. The resistance index（ RI） to BTZ was 17. 84,and higher than that of other chemotherapeutic drugs. Icaritin inhibited the proliferation and induced the apoptosis of KM3/BTZ cells. The IC50 value of BTZ decreased from 0. 345 μg/ml to 0. 149 μg/ml,and the reversal index was 2. 38（ P〈0. 05）. The expression of Par-4 protein increased in a concentration-dependent manner,while the expression of HSP27 and P-gp were down-regulated. Conclusion： Icaritin can inhibit cell proliferation and induce apoptosis of KM3/BTZ cells,moreover,can effectively reverse the multidrug resistance of KM3/BTZ cells. The mechanism may be related with down-regulation of HSP27 and P-gp expression,and up-regulation of Par-4 expression.

关 键 词：淫羊藿素 多发性骨髓瘤 硼替佐米 多药耐药 

分 类 号：R733.3[医药卫生—肿瘤] R979.1[医药卫生—临床医学]