Abstract
S-1, a novel oral fluoropyrimidine, is increasingly used for the treatment of human cancer including gastrointestinal carcinomas. Using the 5-FU resistant DLD-1/FU human colon cancer cell xenografts, the present study investigated whether S-1 enhances the therapeutic efficacy of radiation and if so what are the underlying mechanisms. Nude mice bearing tumor xenografts were treated with radiation, S-1, or both. Tumor growth delay was the treatments' endpoint. To determine whether S-1 enhances intrinsic cell radiosensitivity, we performed clonogenic cell survival assay. Also we assessed the expression of thymidylate synthase (TS) using immunohistochemistry assay. While S-1 or 5 Gy were only slightly effective as single agents in delaying tumor growth, the combined treatment was highly effective. Clonogenic cell survival showed that S-1 strongly enhanced cell radiosensitivity. Immunohistochemistry showed that the expression of TS was down-regulated in tumors treated by S-1 plus radiation. Combined S-1 plus radiation treatment resulted in a synergistic effect in the therapy of 5-FU resistant human colon carcinoma xenografts (EF=2.06). The effect could be attributed to the ability of S-1 to increase cell radiosensitivity (EF=1.9) and to the down-regulation of TS involved in cellular processes leading to radio- and (or) chemo-resistance.
Original language | English |
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Pages (from-to) | 465-471 |
Number of pages | 7 |
Journal | Oncology reports |
Volume | 16 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2006 Sep |
Keywords
- Colon cancer
- Radiation
- S-1
ASJC Scopus subject areas
- Oncology
- Cancer Research