Using adriamycin-resistant human small cell lung cancer cells (SBC-3/ADM), which were 30-fold more resistant to adriamycin than the parent cells (SBC-3), the ability of membrane-modifying agents to overcome the drug resistance was analyzed by a soft agar clonogenic assay. SBC-3/ADM was not circumvented by hyperthermia of 42℃ or amphotericin B at a concentration of 50μ M. Verapamil did not enhance the adriamycin cytoxicity in the SBC-3 cells at a concentration of 10μ M, but a 3.2-fold increase in the drug effect occurred in the SBC-3/ADM cells in terms of LD(70). The efflux of intracellular [H(3)] daunomycin from SBC-3/ADM cells was inhibited by verapamil, while the inhibition did not occur in the parent cells. Furthermore, quinidine (50μ M), cepharanthin (10μ M) and chloroquine (50μ M) enhanced the adriamycin cytotoxicity in the SBC-3/ADM cells. These findings suggest that some membrane-modifying agents could partially overcome the acquired resistance to adriamycin in human small cell lung cancer.
human small cell lung cancer cells in culture
ADM resistant subline
reversal of resistance