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Modulation of expression of multidrug resistance gene (mdr‐1) by adriamycin
Author(s) -
Kato Shoko,
Nishimura Junji,
Yufu Yuji,
Ideguchi Hiroshi,
Umemura Tsukuru,
Nawata Hajime
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81269-r
Subject(s) - multiple drug resistance , p glycoprotein , doxorubicin , pharmacology , efflux , gene , drug resistance , incubation , intracellular , gene expression , cancer cell , chemotherapy , cancer , medicine , cancer research , chemistry , biology , genetics , biochemistry
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/ADR 500 ). 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.