Potentiating effect of amphotericin B on five platinum anticancer drugs in human cis-diamminedichloroplatinum (II) sensitive and resistant ovarian carcinoma cells.
We have determined an effect of amphotericin B (AMB), an antifungal drug, on the cytotoxicity of cis-diamminedichloro-platinum (II) (CDDP) and 4 CDDP analogues in a human ovarian carcinoma cell line (NOS2). Intracellular accumulation of CDDP was elevated significantly by treatment with AMB, and AMB significantly potentiated the cytotoxicity of CDDP by MTT assay. Intracellular accumulation of 4 CDDP analogues was also elevated by the treatment with AMB and the order of increasing accumulation rate of platinum drugs was consistent with that of dose modification factor (DMF). AMB also increased the intracellular CDDP accumulation in CDDP resistant cells (NOS2CR), derived from NOS2. The intracellular accumulations of 4 CDDP analogues were elevated slightly by the treatment with AMB in NOS2CR cells. DMFs of 5 platinum drugs in NOS2CR cells, however, were more than those in NOS2 cells. These results indicate that AMB sensitizes NOS2 and NOS2CR cells to platinum drugs, partially due to the increasing intracellular accumulation of these drugs. In addition, CDDP analogues are more effective in NOS2CR cells than CDDP, but the cytotoxicity of CDDP was most potentiated by AMB among the 5 platinum drugs under study.
Kikkawa
F
F
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Kojima
M
M
Oguchi
H
H
Maeda
O
O
Ishikawa
H
H
Tamakoshi
K
K
Mizuno
K
K
Kawai
M
M
Suganuma
N
N
Tomoda
Y
Y
D000666:Amphotericin B / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000633:toxicity*; D016190:Carboplatin / Q000031:analogs & derivatives / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D002999:Clone Cells; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000633:toxicity; D010051:Ovarian Neoplasms; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C058816:DWA 2114; C055425:NK 121; D000666:Amphotericin B; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin