Modulation of expression of multidrug resistance gene (mdr-1) by adriamycin.

Abstract

The acquired resistance to various drugs in cancer is mediated by P-glycoprotein (P-gp) which is encoded by the mdr-1 gene. An increased level of mdr-1/P-gp was demonstrated after chemotherapy administered to treat cancer in humans. To clarify the direct effect of anticancer drugs on mdr-1/P-gp expression, we investigated the change in transport of adriamycin (ADR), and the expression of the mdr-1 gene and P-gp in an ADR-treated, multidrug-resistant leukemic cell line (K562/ADR500). The addition of ADR induced the over-expression of mdr-1/P-gp, which led to a transient decrease in the intracellular accumulation of ADR although the difference was not statistically significant. A maximal effect was observed after 4 h incubation, returning to the baseline level after further incubation for 12-24 h. The phosphorylation of P-gp was inversely correlated with the levels of P-gp. These observations suggest that ADR itself modulates both the expression and function of P-gp. Determination of the optimal schedule for administering adriamycin is essential to achieving the optimal effect in treating cancer.

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@article{Kato1992ModulationOE, title={Modulation of expression of multidrug resistance gene (mdr-1) by adriamycin.}, author={Shingo Kato and Junji Nishimura and Yuji Yufu and Hiroshi Ideguchi and Takashi Umemura and Hajime Nawata}, journal={FEBS letters}, year={1992}, volume={308 2}, pages={175-8} }