Gefitinib, an epidermal growth factor receptor blockade agent, shows additional or synergistic effects on the radiosensitivity of esophageal cancer cells in vitro

Naruto Taira, Hiroyoshi Doihara, Tetsuya Oota, Fumikata Hara, Tadahiko Shien, Hirotoshi Takahashi, Seiji Yoshitomi, Youichi Ishibe, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 μM to 36.9 μM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy. Copyright

Original languageEnglish
Pages (from-to)25-34
Number of pages10
JournalActa medica Okayama
Volume60
Issue number1
Publication statusPublished - Feb 2006

Keywords

  • Epidermal growth factor receptor
  • Esophageal cancer
  • Gefitinib
  • Radiosensitivity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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