Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists

Abstract

Daunorubicin transport was compared in P388 murine leukemia and in P388/Adramycin (ADR), an anthracycline-resistant subline. We can demonstrate an energy-dependent outward transport system in P388/ADR which limits drug accumulation. Although no calcium requirement for the outward transport process could be shown, several calcium antagonists inhibited outward transport of daunorubicin in P388/ADR and modified the drug resistance pattern. But these agents failed to alter calcium fluxes in either cell line, suggesting that their mode of action in these studies was not related to interactions with calcium-dependent processes. Accumulation differences could not account for the level of daunorubicin resistance observed in the P388/ADR cell line, nor could resistance be wholly circumvented by calcium antagonists.