S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU

Eiko Nakata, Masakazu Fukushima, Yoshihiro Takai, Kenji Nemoto, Yoshihiro Ogawa, Takuma Nomiya, Yasuhiro Nakamura, Luka Milas, Shogo Yamada

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)465-471
    Number of pages7
    JournalOncology reports
    Volume16
    Issue number3
    DOIs
    Publication statusPublished - 2006 Sep

    Keywords

    • Colon cancer
    • Radiation
    • S-1

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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