槲皮素逆转白血病细胞株HL-60/ADM多药耐药的研究  

Reversal of multidrug resistance of HL 60 adriamycin resistant leukemia cell line by quercetin and its mechanisms

作　　者：蔡讯[1] 陈芳源[2] 韩洁英[2] 顾春红[2] 钟华[2] 滕晔[2] 欧阳仁荣[2] 

机构地区：[1]上海交通大学附属第六人民医院肿瘤内科,200233 [2]上海第二医科大学附属仁济医院血液科上海血液学研究所白血病研究室

出　　处：《中华肿瘤杂志》2005年第6期326-329,共4页Chinese Journal of Oncology

基　　金：上海市科委基金资助项目(994319228);上海市卫生局基金资助项目(98418)

摘　　要：目的探讨槲皮素(Que)逆转白血病细胞多药耐药在膜转运蛋白方面的机制。方法通过四唑蓝体外药敏法,检测Que对柔红霉素(DNR)的增敏作用,并以不同浓度作用于HL260/ADM耐药株及相应敏感株HL260;运用逆转录多聚酶链式反应和流式细胞术,检测HL260/ADM和HL260细胞株多药耐药相关基因1(MRP1)及其膜蛋白产物MRP1蛋白的表达情况;借助激光共聚焦显微镜,观察DNR在亚细胞水平的分布变化。结果20～40μmol/L终浓度的Que在体外能明显提高DNR对HL260/ADM耐药株的敏感性,并能下调MRP1基因及其膜蛋白产物MRP1的表达,使DNR回归于细胞核内,从而逆转多药耐药,而且对细胞本身无明显毒性作用。结论Que有可能成为蒽环类药物治疗白血病的有效且低毒的化疗增敏剂。Objective Quercetin, a widely distributed natural flavonoid with a variety of biological functions, can reverse multidrug resistance (MDR) in leukemia according to recent researches. The aim of this study was to investigate the mechanisms of reversal of multi drug resistance by quercetin mainly in respect of membrane transporters. Methods MTT cell viability assay was used to verify the chemo sensitization to daunorubicin (DNR) by quercetin in HL 60/ADM cell line and determine the effective reversal concentration, the expression of MRP 1 gene and its protein product, multidrug resistant associated protein 1 by RT PCR and flow cytometry By confocal laser scanning microscopy,the subcellular distribution of DNR in HL 60/S and HL 60/ADM cells was examined before and after quercetin exposure. Results Compared with HL 60/S,20～40 μmol/L quercetin in vitro remarkably enhanced the sensitivity of HL 60/ADM cells to daunorubicin,down regulated the expression of MRP 1 gene and its protein product MRP 1,restored the abnormal subcellular distribution of daunorubicin,so as to reverse MDR. Moreover, such an effective concentration of quercetin was non toxic to the cells. Conclusion Quercetin could be a candidate of effective multidrug resistance reversing agent with low toxicity in leukemia chemotherapy.

关 键 词：槲皮素 白血病细胞 多药耐药 膜转运蛋白 

分 类 号：R733.7[医药卫生—肿瘤]