洛美利嗪衍生物CJZ3对K562/DOX细胞阿霉素耐药的逆转作用  

Reversal of resistance to doxorubicin by CJZ3,a lomerizine amlodipine derivative,in doxorubicin-resistant human myelogenous leukemia(K562/DOX) cells

作　　者：姬汴生[1] 岳淑梅[1] 何玲[2] 

机构地区：[1]河南大学药物研究所,河南开封475001 [2]中国药科大学药理学教研室,江苏南京210009

出　　处：《中国药理学通报》2007年第11期1431-1436,共6页Chinese Pharmacological Bulletin

基　　金：国家高技术研究发展计划(863计划)资助项目(No2002AA2Z343E);江苏省自然科学基金资助项目(NoBK2004110)

摘　　要：目的研究洛美利嗪衍生物CJZ3对K562/DOX细胞阿霉素耐药的逆转作用。方法应用流式细胞仪和MTT法观察了CJZ3对K562/DOX细胞P-糖蛋白(P-glycoprotein,P-gp)的抑制作用及对K562/DOX细胞阿霉素耐药的逆转作用。结果CJZ3能剂量相关性地增加K562/DOX细胞对罗丹明123(rhodamine123,Rh123)的摄取以及细胞内罗丹明Rh123的累计,明显抑制P-gp介导的Rh123外排,增强阿霉素对K562/DOX细胞的细胞毒作用,提高阿霉素诱导的K562/DOX细胞凋亡率,提高细胞Caspase-3活性,增加K562/DOX细胞内阿霉素水平。结论洛美利嗪衍生物CJZ3体外能明显抑制P-gp的外排功能,逆转P-gp介导的K562/DOX细胞的多药耐药性。Aim To investigate the reversal of resistance to doxorubicin by CJZ3,a lomerizine derivative,in doxorubicin-resistant human myelogenous leukemia（K562/DOX）cells.Methods The effect of CJZ3 on P-glycoprotein（P-gp）function and resistance to doxorubicin in K562/DOX cells were observed by using flow cytometry and MTT assay.Results CJZ3 increased intracellular uptake and accumulation of rhodamine123（Rh123）in K562/DOX cells in a concentration-related manner,significantly inhibited the efflux of Rh123 from the cells,and increased the doxorubicin-induced cytotoxicity,apoptosis rate,Caspase-3 activity in doxorubicin-treated cells and the intracellular accumulation of doxorubicin.Conclusions The reversed effect of CJZ3 on resistance to doxorubicin in K562/DOX cells was associated with its inhibitory effect on P-gp function in vitro.

关 键 词：CJZ3 P-糖蛋白 多药耐药 阿霉素 逆转作用 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R341.32[医药卫生—基础医学]