[Establishment of a cisplatin-resistant human ovarian cancer cell line and the mechanism of resistance].

A cisplatin-resistant cell line was established by using KF-1 cells derived from human serous cystadenocarcinoma of the ovary. This resistant cell line, designated "KFr", was capable of proliferating in the presence of 1.0 microgram/ml cisplatin. It had doubling times of 24.8 and 27.2 hr in the presence of 0.5 and 1.0 microgram/ml cisplatin, respectively. The morphologic characteristics of the KFr cells were an enlarged nucleus and prominent nucleoli, unlike the nucleus and nucleoli of the parent KF-1 cells. The degree of resistance to cisplatin of the KFr cells was about 20 times as great as that of the KF-1 cells, with regard to the concentrations of cisplatin required for 50% inhibition of cell proliferation. Although the cisplatin content in the KF-1 cells incubated with 10 micrograms/ml cisplatin was increased in a time-dependent manner, that in the KFr cells reached the plateau level after 1.5 hr incubation with cisplatin. After about 4 hr incubation, the cellular content in the KFr cells was about a half of that in the KF-1 cells. When 0.5 mg cisplatin was administered i.p. to nude mice with KF-1 or KFr tumor, the cisplatin content in the KFr tumor was significantly lower than that in the KF-1 tumor. The KFr cells showed a cross-resistance to melphalan, while no cross-resistance to vincristine or 5-fluorouracil was observed. When 5 microM W-5 or W-7 was added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited. These findings suggest that the cisplatin resistance in the KFr cells may be due to an impaired cisplatin-transport mechanisms and can be overcome by calmodulin antagonists.