[Effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of Tegafur and UFT (Tegafur plus uracil)].

The effect of calmodulin antagonists (W-5 and W-7) on antitumor activity of 1-(2-Tetrahydrofuryl)-5-fluorouracil (Tegafur; FT) and FT plus uracil (UFT) was examined by using nude mice bearing human ovarian carcinoma (KF cells). All nude mice developed a palpable tumor 17 days after KF cell inoculation unless treatment was done. A combination of UFT and calmodulin antagonists (W-5 or 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 volume in the treatment groups combined with calmodulin antagonists was significantly less than in those in the untreated group after 31 days of tumor inoculation. In addition, tumor volume in a UFT plus W-7 treated group was significantly less than those not only in the untreated group but also in the UFT alone, FT alone, W-5 alone and W-7 alone treated groups, suggesting a synergistic inhibitory effect on tumor growth. The longest median survival time was also observed in a UFT plus W-7 treated group. 5-Fluorouracil (5-FU) content in the tumor of groups treated with FT plus W-5 or W-7 was similar to that in a group treated with FT alone. On the other hand, that of a group treated with UFT plus W-7 was about 2-fold higher than that of a UFT -only treated group.(ABSTRACT TRUNCATED AT 250 WORDS)