槲皮素逆转白血病细胞株K562/ADM多药耐药的研究  

Study on the mechanism of multi-drug resistance reversed by quercetin in leukemic K562 adriamycin resistant cell lines

作　　者：蔡讯[1] 陈芳源[1] 韩洁英[1] 顾春红[1] 钟华[1] 滕晔[1] 欧阳仁荣[1] 

机构地区：[1]上海第二医科大学附属仁济医院血液科,上海200001

出　　处：《肿瘤》2004年第4期354-357,共4页Tumor

基　　金：上海市科委基金资助项目 (编号 :9943 19228);上海市卫生局基金资助项目(编号 :98418)

摘　　要：目的　探讨槲皮素逆转白血病细胞多药耐药在膜转运蛋白方面的机制。方法　通过MTT体外药敏法证明槲皮素对柔红霉素的增敏作用并确定逆转的浓度范围 ,作用于K5 6 2 /ADM耐药株及相应敏感株K5 6 2 /S ,运用逆转录多聚酶链式反应(RT PCR)和流式细胞术检测多药耐药基因 (Mdr1)及其膜蛋白产物P 170糖蛋白 (P gp)的表达情况 ,在激光共聚焦显微镜观察柔红霉素在亚细胞水平的分布变化。结果　 2 0～ 4 0 μmol/L终浓度槲皮素在体外能明显提高柔红霉素对K5 6 2 /ADM耐药株的敏感性 ,并能下调Mdr1基因及其膜蛋白产物P gp的表达 ,恢复柔红霉素在亚细胞水平的异常分布 ,回归其作用靶点———细胞核 ,从而逆转多药耐药 ,且有效浓度范围的药物对细胞本身无毒性作用。Objective To investigate the mechanism of multi-drug resistance(Mdr) reversed by Quercetin mainly in respect of membrane transporters. Methods MTT cell viability assay was adapted for verifying the chemo-sensitization of Quercetin to Daunorubicin(DNR), and the reverse concentration was determined. The expression of Mdr1 gene and its protein product P-glycoprotein(P-gp) were analysed by RT-PCR and flow cytometry with monoclonal antibody. By confocal laser scanning microscopy,the subcellular distribution of DNR in K562/S and K562/ADM cell lines was observed before and after exposing to Quercetin. Results Comparing with K562/S,20～40μmol/L Quercetin in vitro can remarkably increase the sensitivity of K562/ADM to DNR,down-regulate the expression of Mdr1 gene and its protein product P-gp,restore the abnormal subcellular distribution of DNR,so as to reverse multidrug resistance. Conclusion Quercetin may become a candidate of effective multi-drug resistance-reversing agent with low toxicity in leukemia chemotherapy.

关 键 词：槲皮素 白血病细胞株 KS62/ADM 多药耐药性 MDRL基因 P-糖蛋白 

分 类 号：R733.7[医药卫生—肿瘤]