[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, harringtonine, mitomycin C, doxorubicin, epirubicin, 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 intracellular uptakes of these drugs at 2 h were reduced 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 K562r 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.