[Anti-metastatic and anti-angiogenic activity of UFT in a lung spontaneous metastasis model in mice].

We investigated the effect of UFT on a pulmonary metastasis after excision of the primary lesion, which was induced by implantation of murine renal carcinoma cells, RENCA. The cells were implanted into the left kidney of Balb/cA mice, and nephrectomy of the left kidney with a primary tumor was performed on day 10 after implantation. Administration of antitumor drugs, was started on day 13 [UFT (20 mg/kg, p.o., 5'-DFUR (24.6 mg/kg, p.o.), 5-FU (19 mg/kg, i.v.), TNP-470 (30 mg/kg, s.c.)]. In this metastasis model, the estimated mean survival time of the control group was 41.3 +/- 2.9 days. A significant life-prolonging effect was observed for UFT and 5-FU (T/C: 160.8%, 125.7%, respectively). An inhibitory effect on the growth of metastatic tumors in the lung was detected for both UFT and TNP-470 (TWI: 55.5%, 48.7%, respectively), but not 5'-DFUR. In a dorsal air sac (DAS) model, UFT abrogated angiogenesis induced by RENCA in a dose-dependent manner. These data suggest that the life-prolonging effect of UFT results from the continuous exposure of a tumor to its cytotoxic effects and anti-angiogenic activity.