槲皮素对白血病细胞中膜转运蛋白的调节作用

Regulation of Mdr1, MRP1 gene and their protein products P-glycoprotein, multid rug resistance associated protein 1 in leukemic cells by Quercetin

目的 探讨槲皮素对白血病细胞中膜转运蛋白的调节作用。方法 通过四唑蓝 (MTT)体外药敏法证明槲皮素对柔红霉素的增敏作用 ,作用于K5 6 2 /ADM和HL 6 0 /ADM耐药株及相应敏感株K5 6 2 /S和HL 6 0 /S ,采用RT PCR和流式细胞术检测多药耐药基因 (Mdr1)和多药耐药相关基因 1(MRP1)及其膜蛋白产物P 170糖蛋白 (P gp)和MRP1蛋白的表达情况。 结果 终浓度为 2 0～ 4 0 μmol/L的槲皮素在体外能明显提高柔红霉素对K5 6 2 /ADM和HL 6 0 /ADM耐药株的敏感性 ,并能下调Mdr1和MRP1基因及其膜蛋白产物P gp和MRP1蛋白的表达 ,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 regulation of membrane transporters in leukemic cells by quer cetin.Methods MTT cell viability assay was adopted for verifying the chemosensitization of Q u ercetin to Daunorubicin (DNR) in K562/ADM and HL-60/ADM cells and the reverse c oncentration was determined, then the expression of Mdr1, MRP1 gene and their pr o tein products P-glycoprotein (P-gp) and multidrug resistance associated protei n 1 (MRP1) were analysed by RT-PCR and flow cytometry using monoclonal antibody before and after exposure to Quercetin. Results Comparing with K562/S, 20～40 μmol/L Quercetin in vitro could remarkably inc rease the sensitivity of K562/ADM to DNR and down-regulate the expression of Md r1, MRP1 gene and their protein products P-gp and MRP1, so as to reverse the multi drug resistance. Conclusion Quercetin may become a candidate of effective multi-drug resistance-rev ersing agent with low toxicity for leukemia chemotherapy.