甲诺孕酮与甲地孕酮逆转P糖蛋白介导的多药耐药性的比较研究  

COMPARATIVE STUDY OF REVERSAL EFFECT OF NOMEGESTROL ACE TATE AND MEGESTROL ACETATE ON P GLYCOPROTEIN INDUCED MULTIDRUG RESISTANCE

作　　者：李杰[1,2] 许良中[1,2] 何开玲[1,2] 朱伟萍 张泰明[1,2] 郑云红 夏鹏[1,2] 

机构地区：[1]上海医科大学肿瘤医院分子病理研究室 [2]上海医科大学药学院有机化学教研室

出　　处：《肿瘤》1998年第6期400-402,共3页Tumor

摘　　要：目的比较甲诺孕酮（ＮＯＭ）与甲地孕酮（ＭＧ）对Ｋ５６２耐阿霉素（ＡＤＭ）细胞株（Ｋ５６２／ＡＤＭ）ｍｄｒ１基因的调节。方法应用细胞培养、ＭＴＴ比色、免疫组织化学、ＲＴ┐ＰＣＲ和流式细胞技术进行分析。结果ＮＯＭ确有逆转作用，逆转活性与ＭＧ相似，并可下调ｍｄｒ１表达，调节呈时间依赖性。结论ＮＯＭ可明显逆转Ｐ糖蛋白介导的Ｋ５６２／ＡＤＭ的ＭＤＲ，因其毒性作用轻微，有可能成为较好的新型逆转剂。Objective:To study modulation of mdr1 by nomegestrol acetate(NOM) in K562 cell line, as compared with megestrol acetate(MG).Methods:Adriamycin(ADM) resistant K562(K562/ADM) and parental K562(K562/S) were treated with NOM or MG.The alterations of chemosensitivity to ADM were evaluated by MTT assays,mRNA and protein of mdr1 gene depression by RT PCR and immunohistochemistry,and accumulation of ADM by flow cytometry(FCM).Results:Both NOM and MG markedly enhance chemosensitivity to ADM in K562/ADM.After 20 μmol,10 μmol and 5μmol of reversal drugs treatment,the chemosenstivity to ADM increased 18.6,14.1 and 5.3 times respectively in NOM treated cells, and 16,14.5 and 5 times respectively in MG treated cells.FCM assays showed that both drugs treated cells increased accumulation of ADM by 3～4 times.The reversal activity of NOM was similar to that of MG,both NOM and MG were found to inhibit mdr1 expression at the level of mRNA and protein.This modulation on gene expression was time dependent and the maximal effects appeared after 5 days of drug treatment.Conclusion:NOM markedly reverses P glycoprotein induced MDR of K562/ADM.NOM was effective as MG.Both drugs can modulate mdr1 expression in a time dependent manner.Since NOM have low toxicity,they might be used as good reversal agents.

关 键 词：多药耐药性 甲诺孕酮 甲地孕酮 阿霉素 P糖蛋白 

分 类 号：R977.12[医药卫生—药品] R979.14[医药卫生—药学]