Establishment of a Cisplatin-Resistant Human Ovarian Cancer Cell Line2

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Abstract
A cisplatin-resistant cell line was established by use of 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 μg cisplatin/ml. It had doubling times of 24.8 and 27.2 hours in the presence of 0.5 and 1.0 μg cisplatin/ml, respectively. The KFr cells had lactate dehydrogenase (LDH) activities about fourfold higher than those of the parent KF-1 cells. Analysis of the isozymes of the KFr cells revealed that they had a faint LDH-3 band in addition to LDH-4, the only stained band in the parent KF-1 cells. 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 twenty-fold higher than that of the KF-1 cells, with regard to the concentrations of cisplatin required for 50% inhibition of cell proliferation. However, when 5 μM calmodulin antagonists [N-(6-aminohexyl)-1-naphthalenesulfonamide or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] were added in the presence of concentrations of cisplatin that hardly inhibited cell proliferation, the KFr cell proliferation was markedly inhibited. These results suggest that cisplatin resistance can be overcome by calmodulin antagonists.