槲皮素对多药耐药白血病细胞株K562/ADM和HL-60/ADM中柔红霉素亚细胞分布的恢复作用
[Restorative effect of quercetin on subcellular distribution of daunorubicin in multidrug resistant leukemia cell lines K562/ADM and HL-60/ADM].
作者信息
Cai Xun, Chen Fang-Yuan, Han Jie-Ying, Gu Chun-Hong, Zhong Hua, Ouyang Ren-Rong
机构信息
Department of Oncology, Shanghai No. 6 People's Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China.
出版信息
Ai Zheng. 2004 Dec;23(12):1611-5.
BACKGROUND & OBJECTIVE: Quercetin, a widely distributed natural flavonoid with a variety of biological functions, can reverse multidrug resistance (MDR) in leukemia according to recent researches. This study was to investigate the mechanism of quercetin restoring subcellular distribution of daunorubicin (DNR) in multidrug resistant leukemia cell lines, K562/ADM and HL-60/ADM, and reversing their MDR.
METHODS
MTT cell viability assay was used to verify the sensitization of DNR by quercetin in K562/ADM and HL-60/ADM cells,and determine the reverse concentration extent,confocal laser scanning microscope was used to observe the subcellular distribution of DNR in K562/ADM and HL-60/ADM cells,and relevant sensitive cell lines, K562/S and HL-60/S,before and after quercetin exposion.
RESULTS
Compared with K562/S and HL-60/S cells,20-40 micromol/L of quercetin in vitro remarkably enhanced the sensitivity of K562/ADM and HL-60/ADM cells to DNR, restore the subcellular distribution of DNR, so as to reverse MDR.
CONCLUSION
quercetin could be a candidate of effective multidrug resistance-reversing agent in leukemia chemotherapy.
背景与目的
槲皮素是一种广泛分布且具有多种生物学功能的天然黄酮类化合物，近期研究表明其可逆转白血病中的多药耐药性（MDR）。本研究旨在探讨槲皮素恢复多药耐药白血病细胞系K562/ADM和HL-60/ADM中柔红霉素（DNR）亚细胞分布并逆转其MDR的机制。
方法
采用MTT细胞活力测定法验证槲皮素对K562/ADM和HL-60/ADM细胞中DNR的增敏作用，并确定逆转浓度范围；采用共聚焦激光扫描显微镜观察槲皮素作用前后K562/ADM和HL-60/ADM细胞以及相关敏感细胞系K562/S和HL-60/S中DNR的亚细胞分布。
结果
与K562/S和HL-60/S细胞相比，体外20 - 40 μmol/L的槲皮素显著增强了K562/ADM和HL-60/ADM细胞对DNR的敏感性，恢复了DNR的亚细胞分布，从而逆转MDR。
结论
槲皮素可能成为白血病化疗中有效的多药耐药逆转剂候选药物。
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