Combined effects of the oral fluoropyrimidine anticancer agent, S-1 and radiation on human oral cancer cells

We evaluated the orally administered S-1, in combination with ionizing radiation both in vivo and in vitro against human oral cancer cell lines. Human oral cancer cell tines were used as subcutaneous xenografts in nude mice. S-1 (10 mg/kg) was administered orally 1 h before radiation treatments (1.5 Gy), or 1 h after radiation for five consecutive days. Apoptotic cells were detected by TUNEL method. For in vitro analysis, attached cells were treated with S-1 (50 mug/ml) for 1 h and then irradiated (3, 6, 9, 12, 15 Gy), or they were treated with S-1 for 1 h after radiation. Cell survival was determined by clonogenic assay. The combination of S-1 and radiation was more effective than either agent atone. In addition, S-1 administration before radiation was more effective than S-1 administration after radiation. Moreover, the combination of S-1 and radiation could induce apoptosis significantly than either agent alone (P < 0.01). In vitro clonogenic survival experiments demonstrated the dose enhancement ratio of 1.22 (radiation + S-1), 1.45 (S-1 + radiation) in B88 cells, and 1.16 (radiation + S-1), 1.28 (S-1 + radiation) in HSG cells. These data demonstrate that the combination of S-1 and fractionated radiotherapy is more effective against human oral cancer xenografts than either agent atone, and that S-1 administration before radiation is more effective than after radiation, suggesting a potential clinical applicability of combination treatment of S-1 and radiation in oral cancer therapies. (C) 2004 Published by Elsevier Ltd.