Reversal effects of droloxifene on multidrug resistance in adriamycin-resistant K562 cell line  

屈洛昔芬对K562耐阿霉素细胞株耐药性的逆转作用(英文)

作　　者：李杰 许良中[1] 药锦娟[1] 郭伟剑[2] 夏鹏[3] 陈瑛[3] 

机构地区：[1]上海肿瘤医院分子病理研究室,上海200032 [2]上海第二医科大学附属新华医院肿瘤中心肿瘤科,上海200092 [3]复旦大学药学院有机合成系,上海中国200032

出　　处：《Acta Pharmacologica Sinica》2001年第11期1023-1027,共5页中国药理学报（英文版）

摘　　要：AIM: To study the reversal effects of droloxifene (DRO) on multidrug resistance (MDR) in K562 cell line resistant to adriamycin (ADR). METHODS: K562 cell line resistant to ADR (K562/A02) and K562 cell line sensitive to ADR (K562) were treated with DRO. Using MIT assay, chemosensitivity to ADR in DRO-treated K562 cell lines was studied. Before and after the treatment with DRO 10μmol/L, MDR1 and GSTπ gene expression were assayed by reverse transcription-polymerase chain reaction and immunocytochemistry assay. Flow cytometry was used to determine intracellular ADR concentration. RESULTS: DRO significantly reversed MDR in K562/A02 (P < 0.01). After treatment of DRO 20, 10, and 5 μmol/L, the chemosensitivity to ADR was increased to 14, 13, and 4 folds, respectively. The reversal activity of DRO was similar to that of verapamil (VRP). After treated with DRO 10 μmol/L, both MDR1 and GSTπ mRNA expression began to decline on the 2nd day, and significantly decreased on the 5th day (P <0.01). The changes in P-gp and GSTπ protein expression were similar to that of their mRNA expression. Two hours after treatment of DRO 20, 10, and 5 μmol/L, intracellular ADR concentration in K562/A02 was increased to 2. 9, 2. 3, and 1. 5 folds, respectively. However, DRO did not markedly increase ADR accumulation in K562. CONCLUSION: DRO had strong reversal effect on MDR in K562/A02, which was comparable to that of VRP, but the reversal effect was viadifferent pathways.目的:研究屈洛昔芬(DRO)对耐阿霉素(ADR)K562细胞株(K562/A02)多药耐药性(MDR)的逆转作用及逆转机制。方法:用DRO分别处理K562/A02和K562敏感株。MTT法观察DRO影响K562/A02对ADR化学敏感性的变化。DRO 10μmol/L处理K562/A02前后,通过RT-PCR和免疫细胞化学染色,分析MDR1、GSTπ基因表达的变化,采用流式细胞技术测定细胞内ADR浓度的变化。结果:DRO显著逆转K562/A02的MDR,在20、10和5μmol/L浓度时,对ADR的化学敏感性分别增加到14、13和4倍,逆转活性与维拉帕米相当。MDR1和GSTπ的mRNA和蛋白表达在DRO 10μmol/L处理后第2天开始下降,第5天明显降低。用20、10和5μmol/L浓度的DRO处理两株细胞,K562/A02细胞内ADR积累分别增加到2.9、2.3和1.5倍。但DRO不能明显增加K562细胞内的ADR的浓度。结论:DRO对K562/A02的MDR有较强的逆转活性,逆转强度与维拉帕米相当,其逆转机制有多种不同的途径。

关 键 词：K562 cells DROLOXIFENE multiple drug different pathways resistance 

分 类 号：R96[医药卫生—药理学]