Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells

  • Authors:
    • Kazumasa Fukuda
    • Yoshiro Saikawa
    • Masashi Takahashi
    • Tsunehiro Takahashi
    • Norihito Wada
    • Hirohumi Kawakubo
    • Hiroya Takeuchi
    • Yuko Kitagawa
  • View Affiliations

  • Published online on: December 1, 2011     https://doi.org/10.3892/ijo.2011.1279
  • Pages: 975-982
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Abstract

Overexpression of human epidermal growth factor receptor (EGFR) has been detected in gastric cancer (GC) and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting agents and cytotoxic agents are considered to be a potential therapeutic option for EGFR-overexpressing GC. Herein, we have investigated the effects of combination treatment with the oral fluoropyrimidine S-1 and the EGFR-targeting agent cetuximab in GC cells with or without EGFR overexpression. EGFR expression was determined by FACS and quantitative PCR in GC cells. Experimental 5-fluorouracil (5FU) was used instead of S-1 for in vitro experiments. The efficacy of 5FU or cetuximab monotherapy or combination 5FU/cetuximab therapy was examined in vitro and in vivo. Clinical specimens were examined for EGFR by immunohistochemistry (IHC). EGFR expression score was defined as strong membrane and cytoplasmic staining in at least 50-75% of cells. The combination of 5FU and cetuximab synergistically inhibited cell proliferation and exhibited an enhanced proapoptotic effect in GC cells with EGFR overexpression. Cetuximab also induced down-regulation of phosphorylation of EGFR and AKT, leading to diminished signaling. The antitumor effect of the combi­nation of S-1 and cetuximab in vivo was also greater than that of either drug alone. Our preclinical findings thus indicate that the combination of S-1 and EGFR-targeting therapy is a promising treatment option for GC with EGFR overexpression.
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April 2012
Volume 40 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Fukuda K, Saikawa Y, Takahashi M, Takahashi T, Wada N, Kawakubo H, Takeuchi H and Kitagawa Y: Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells. Int J Oncol 40: 975-982, 2012
APA
Fukuda, K., Saikawa, Y., Takahashi, M., Takahashi, T., Wada, N., Kawakubo, H. ... Kitagawa, Y. (2012). Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells. International Journal of Oncology, 40, 975-982. https://doi.org/10.3892/ijo.2011.1279
MLA
Fukuda, K., Saikawa, Y., Takahashi, M., Takahashi, T., Wada, N., Kawakubo, H., Takeuchi, H., Kitagawa, Y."Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells". International Journal of Oncology 40.4 (2012): 975-982.
Chicago
Fukuda, K., Saikawa, Y., Takahashi, M., Takahashi, T., Wada, N., Kawakubo, H., Takeuchi, H., Kitagawa, Y."Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells". International Journal of Oncology 40, no. 4 (2012): 975-982. https://doi.org/10.3892/ijo.2011.1279