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Enhancement of Antineoplastic Effects of Cisplatin by Calmodulin Antagonists in Nude Mice Bearing Human Ovarian Carcinoma¹

Department of Obstetrics and Gynecology, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359, Japan

The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide(W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5)] in nude mice bearing human ovarian carcinoma. Tumor growth of nude mice treated with W-7 or W-5 combined with cisplatin was significantly inhibited, compared to that of nude mice treated with W-7 alone, W-5 alone, or cisplatin alone. Although treatment with cisplatin alone markedly inhibited lytic activity of spleen cells from tumor-bearing nude mice against the tumor cells, the inhibitory effect was eliminated by combination with W-7 or W-5. There was no significant difference in survival time among untreated, cisplatin-treated, W-7-treated, and W-5-treated groups. Only when cisplatin was followed by W-7 or W-5 was a significant enhancement by W-7 or W-5 of the antitumor effect of cisplatin observed with respect to inhibition of tumor growth as well as prolongation of survival time.

¹ Supported in part by a grant from the Special Scientific Research Program of the Defense Agency in Japan.

² To whom requests for reprints should be addressed.

Received 6/18/86. Revised 2/26/87. Revised 7/29/87. Accepted 9/ 9/87.