Adaptive response towards adriamycin in vitro: circumvention with verapamil.
In an attempt to identify mechanisms of adaptive response to adriamycin (ADR), we have earlier isolated ADR-resistant cell lines CHO/R and ME18/R by short-term pulse exposures of parent cell lines to this drug, followed by single-cell cloning. The results presented in this study have shown that the development of resistance to ADR was accompanied by cross-resistance to vinblastine and methotrexate. The resistance of tested cell lines towards ADR was substantially reversed by verapamil (VPL) at non-toxic concentrations. VPL abolished also the capability of these cell lines to express adaptive response after treatment of the cells with a conditioning dose of ADR. From the results of our study, we conclude that similar characteristics play a role in the mechanism of the phenomenon of adaptive response as in the mechanism of pleiotropic multidrug resistance.
Anuszewska
E L
EL
Drug Institute, Warsaw, Poland.
Koziorowska
J H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy; D008727:Methotrexate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D004338:Drug Combinations; D014747:Vinblastine; D004317:Doxorubicin; D014700:Verapamil; D008727:Methotrexate