5-fluorouracil (5-FU) and its analogues have been widely prescribed for patients in Japan with gastrointestinal cancers. The active metabolite of 5- FU inhibits thymidylate synthase (TS), resulting in the inhibition of DNA synthesis. However, the process of cell death after the inhibition of DNA synthesis has not been elucidated. In this issue, we investigated antitumor activity of 5-FU and influence on the cell cycle of two different cell lines in vitro, and also examined the induction of apoptosis in seven xenografts in vivo by oral analogue of 5-FU, tegafur and uracil (UFT: a combined preparation of 1 mol tegafur and 4 mol uracil). Though the TS levels in two cell lines were not so different, sensitivities to 5-FU were remarkably different in vitro. The seven xenografts have various sensitivities to UFT, and there was a positive correlation between the extent of apoptotic induction and the anti-tumor effect of UFT. Spontaneous apoptosis observed in untreated tumor xenografts also correlated with the anti-tumor effect of the UFT as well as the apoptosis induced in tumor xenografts treated with the agent. Our results showed that apoptosis in a tumor reflects well anti-tumor drug sensitivity, and it may serve as a predictor of 5-FU effectiveness.
|Number of pages
|Published - 1998
All Science Journal Classification (ASJC) codes
- Cancer Research