Hargrave R M, Davey M W, Davey R A, Kidman A D
Neurobiology Unit, University of Technology, Sydney, NSW, Australia.
Anticancer Drugs. 1995 Jun;6(3):432-7. doi: 10.1097/00001813-199506000-00011.
Multidrug resistance (MDR) is associated with poor prognosis in leukemia, and anthracyclines, which are used in the treatment of leukemia, are associated with the expression of P-glycoprotein and the development of MDR. We report here that idarubicin, a new anthracycline approved for use in the treatment of acute myelogenous leukemia (AML), did not induce P-glycoprotein expression in the K562 human leukemia cell line under conditions where daunorubicin, doxorubicin and epirubicin did induce expression of P-glycoprotein. The P-glycoprotein expressing, multidrug resistant sublines developed to daunorubicin (K/DNR), doxorubicin (K/DOX) and epirubicin (K/EPR) were cross-resistant to the other anthracyclines and to vinblastine, taxol, colchicine and actinomycin D, but were not resistant to idarubicin or etoposide. The idarubicin treated subline, K/IDA, was only resistant to taxol but was 12-fold sensitized to etoposide, suggesting that idarubicin had affected topoisomerase II in this subline.
多药耐药（MDR）与白血病的不良预后相关，而用于治疗白血病的蒽环类药物与P-糖蛋白的表达及MDR的发生有关。我们在此报告，伊达比星是一种已被批准用于治疗急性髓性白血病（AML）的新型蒽环类药物，在柔红霉素、多柔比星和表柔比星可诱导P-糖蛋白表达的条件下，它在K562人白血病细胞系中并未诱导P-糖蛋白表达。对柔红霉素（K/DNR）、多柔比星（K/DOX）和表柔比星（K/EPR）产生的表达P-糖蛋白的多药耐药亚系对其他蒽环类药物以及长春碱、紫杉醇、秋水仙碱和放线菌素D具有交叉耐药性，但对伊达比星或依托泊苷不耐药。经伊达比星处理的亚系K/IDA仅对紫杉醇耐药，但对依托泊苷敏感12倍，这表明伊达比星在该亚系中影响了拓扑异构酶II。
