蒽环类药物在多药抗药细胞株K562r细胞内的积聚、滞留与外排

我们建立的抗药细胞株K 562r表现为典型的MDR特性,K 562r细胞对阿霉素、表阿霉素、及柔红霉素的摄入量减少,外排量增加。维拉帕米对K 562r细胞的药物摄取无明显影响,但能抑制K 562r细胞内的药物外排,摄取药物60min时,1×10~6K 562r细胞核中阿霉素、表阿霉素和柔红霉素的含量分别为809±68,1238±81和1664±77 ng,显著低于K562r细胞核内的药物含量P<0.01。

Intracellular accumulation retention and distribution of anthracyclines in a multidrug- resistant variant K562r

A multidrug resistant variant (K562r) of the human K562 erythroleukemia cell line was obtained in vitro by repeated exposure of these cells to vincristine. The K562r cells were resistant to vincristine, har ringtonine, mitomycin C, doxorubicin, epiru-bicin, and daunorubicin but retained the sensitivity to methotrexate. The resistances to vincristine and anthracyclines were reversed in the presence of verapamil. Despite being 60-or over 60-fold resistances to doxorubicin, epirubicin and daunorubicin, the net intracel-lular uptakes of these drugs at 2 h were re duced by only 15%, 20%, and 11%, respectively in K562r cells compared to their parental line. Verapamil did not enhance drug accumulation but inhibited drug efflux in K562r cells. Though there was no significant difference of drug content in cytoplasm between K562 and K562r cells, the drug content in the nucleus of K 562r cells reduced significantly compared to that in K562 cells. The lower concentrations of anthracyclines in the nucleus of K562r cells might contribute to their acquisition of drug resistance.