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

  • Authors:
    • Eiko Nakata
    • Masakazu Fukushima
    • Yoshihiro Takai
    • Kenji Nemoto
    • Yoshihiro Ogawa
    • Takuma Nomiya
    • Yasuhiro Nakamura
    • Luka Milas
    • Shogo Yamada
  • View Affiliations

  • Published online on: September 1, 2006     https://doi.org/10.3892/or.16.3.465
  • Pages: 465-471
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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.

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September 2006
Volume 16 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Nakata E, Fukushima M, Takai Y, Nemoto K, Ogawa Y, Nomiya T, Nakamura Y, Milas L and Yamada S: S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU. Oncol Rep 16: 465-471, 2006
APA
Nakata, E., Fukushima, M., Takai, Y., Nemoto, K., Ogawa, Y., Nomiya, T. ... Yamada, S. (2006). S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU. Oncology Reports, 16, 465-471. https://doi.org/10.3892/or.16.3.465
MLA
Nakata, E., Fukushima, M., Takai, Y., Nemoto, K., Ogawa, Y., Nomiya, T., Nakamura, Y., Milas, L., Yamada, S."S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU". Oncology Reports 16.3 (2006): 465-471.
Chicago
Nakata, E., Fukushima, M., Takai, Y., Nemoto, K., Ogawa, Y., Nomiya, T., Nakamura, Y., Milas, L., Yamada, S."S-1, an oral fluoropyrimidine, enhances radiation response of DLD-1/FU human colon cancer xenografts resistant to 5-FU". Oncology Reports 16, no. 3 (2006): 465-471. https://doi.org/10.3892/or.16.3.465