[Combination cancer chemotherapy of human gastric and colon carcinomas in nude mice--sequential cancer chemotherapy involving mitomycin C and tegafur]

Abstract

Three human tumor xenografts serially transplanted into nude mice were used for an experimental combination cancer chemotherapy consisting of mitomycin C (MMC) and tegafur (FT-207). The strains used for the experiments were two gastric (St-4 and St-15) and one colon (Co-3) carcinomas. The minimal effective doses of MMC were administered i. p. 24h after the s. c. tumor inoculations followed by 60 mg/kg of FT-207 in the three different modalities i. p. These were (A) daily administration of FT-207, (B) FT-207 only, 24h after MMC treatment and (C) FT-207 only, 5 days after MMC treatment. The antitumor effect assessed by the tumor weight at the end of the experiment was found to be (A) divided by (B) greater than (C), whereas the total administration doses of FT-207 were (A) greater than (B) = (C). As this result suggested the significance of FT-207 given 24h after MMC, flow cytometric analysis of St-15 tumor was conducted 24 and 48 h after the MMC treatment. It was observed that the incidence of 2n cells was depressed and the amount of 4n cells increased by MMC, indicating the recruitment of tumor cells into the proliferating phase. Because these recruited cells were thought to be sensitive to FT-207, it was supposed that the antitumor effect was elevated when FT-207 was given 24h after MMC. This semi-synchronized combination cancer chemotherapy involving MMC and FT-207 might therefore be useful for clinical application.