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

Publisher Website
Google Scholar
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.