Enhancement of antineoplastic effects of cisplatin by calmodulin antagonists in nude mice bearing human ovarian carcinoma.
The present study was designed to potentiate the antineoplastic effects of cisplatin by combination with calmodulin antagonists [N-(6-amino-hexyl)-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.
Kikuchi
Y
Y
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
Oomori
K
K
Kizawa
I
I
Hirata
J
J
Kita
T
T
Miyauchi
M
M
Kato
K
K
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013154:Spleen / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*
D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D002945:Cisplatin