Comparison of the cellular pharmacology of doxorubicin in resistant and sensitive models of pancreatic cancer

Abstract

The cellular accumulation and retention of doxorubicin (ADR) was investigated in two models of pancreatic adenocarcinoma, which differ markedly in their sensitivity to ADR. In vitro studies revealed that the relatively resistant cell line, WD PaCa (or well-differentiated pancreatic adenocarcinoma of the Syrian hamster), actually had higher ADR cellular levels than the sensitive cell line, PD PaCa (or poorly differentiated pancreatic adenocarcinoma of the Syrian hamster). While the efflux of ADR from WD PaCa was greater, the overall retention of ADR by WD PaCa was comparable to PD PaCa. These results failed to document differences in accumulation or retention of ADR capable of explaining the difference in the sensitivity of the cell lines to ADR and indicate the need to search beyond attainable drug concentrations for mechanisms of primary ADR resistance.