Oral administration of uracil-tegafur (UFT) inhibits liver micrometastasis of human colon cancer in an orthotopic nude mouse model and its early detection system.

Abstract

To evaluate the effect of UFT (an oral antineoplastic drug combining uracil and tegafur) as an adjuvant chemotherapy. We examined whether UFT inhibits micrometastasis of the liver from colon cancer implanted into the cecum of nude mice in an orthotopic model. Moreover, we studied whether our early detection system using a polymerase chain reaction (PCR) of the human beta-globin gene would be useful in this model. The administration of 20 mg/kg UFT p.o., which is a relatively small dose compared with 65 mg/kg of the maximum tolerated dose of this drug in mice, inhibited liver metastasis completely when started immediately after a cecectomy (micrometastasis present at this time), but did not inhibit liver metastasis significantly when started at 4 weeks after a cecectomy (gross tumor present at this time). There were no severe toxicities at this dose. In our PCR study, all livers in 10 mice to which therapy was given immediately after a cecectomy and without liver metastasis showed no PCR-amplified fragment, while 7 of 10 livers in the nontreatment group in which gross liver metastases were not observed demonstrated this fragment. These findings indicate that UFT is useful for either adjuvant chemotherapy or the inhibition of micrometastasis, and our system to detect micrometastasis by examining the human beta-globin gene is useful for the early evaluation of the efficacy of these drugs.