Adjuvant effects of calmodulin antagonists on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur) and a mixture of ftorafur and uracil (UFT) in nude mice bearing human ovarian carcinomas.
Effects of N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5) and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on antitumor activity of 1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur, FT) and a mixture of FT and uracil (UFT) were determined in nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed palpable tumor 17 days after KF cell inoculation unless treated. A combination of UFT and calmodulin antagonists (W-5 and W-7) resulted in a delay in tumor formation in nude mice. One of 10 nude mice treated with a combination of UFT and W-5 and 3 of 10 nude mice treated with UFT and W-7 did not develop tumors during the experimental period. Tumor volumes in groups treated with the combinations of UFT and calmodulin antagonists were significantly smaller than those in the untreated group after 31 days of tumor inoculation. In addition, tumor volumes in a group treated with UFT plus W-7 were significantly smaller than not only those in the untreated group but also those in groups treated with UFT alone, FT alone, W-5 alone, or W-7 alone. The longest median survival time was also observed in the group treated with UFT plus W-7. 5-Fluorouracil (5-FU) content of the tumors of groups treated with FT plus W-5 or W-7 was similar to that of the group treated with FT alone. On the other hand, 5-FU content of a group treated with UFT plus W-7 was about twofold higher than that of a group treated with UFT alone. These results suggest that a synergistic effect of W-7 and UFT on inhibition of tumor growth and prolongation of survival time may result from accumulation of 5-FU in the tumor.
Kikuchi
Y
Y
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama, Japan.
Oomori
K
K
Iwano
I
I
Kizawa
I
I
Miyauchi
M
M
Kita
T
T
Kuki
E
E
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013449:Sulfonamides / Q000627:therapeutic use; D005641:Tegafur / Q000627:therapeutic use*; D013997:Time Factors; D014498:Uracil / Q000627:therapeutic use*
D002147:Calmodulin; D004338:Drug Combinations; D013449:Sulfonamides; D005641:Tegafur; D014498:Uracil; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D005472:Fluorouracil