Reversal of cisplatin resistance with amphotericin B in a non-small cell lung cancer cell line.
The potentiation of anticancer agents by non-anticancer drugs is one of the possible strategies for overcoming cellular resistance to chemotherapy. In order to overcome cis-diamminedichloroplatinum(II) (CDDP) resistance, we evaluated the sensitizing effect on CDDP-induced cytotoxicity of various non-anticancer agents which might alter membrane transport, by means of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Drugs which have previously been demonstrated to modify multidrug resistance did not show a sensitizing effect to cisplatin. Only amphotericin B (AmB) selectively conquered CDDP resistance in the CDDP-resistant cell line. A drug accumulation study done by the atomic absorption method demonstrated that the accumulation of CDDP in the resistant cell line recovered to the level of the parental cell line after treatment with AmB. Thus, AmB might overcome CDDP resistance by increasing the accumulation of CDDP.
Morikage
T
T
Pharmacology Division, National Cancer Center Hospital, Tokyo.
Bungo
M
M
Inomata
M
M
Yoshida
M
M
Ohmori
T
T
Fujiwara
Y
Y
Nishio
K
K
Saijo
N
N
D000666:Amphotericin B / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology*; D004357:Drug Synergism; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms
D000666:Amphotericin B; D002945:Cisplatin