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

• Published in: Acta medica Okayama Vol. 60; no. 1; p. 25
• Main Authors: Taira, Naruto, Doihara, Hiroyoshi, Oota, Tetsuya, Hara, Fumikata, Shien, Tadahiko, Takahashi, Hirotoshi, Yoshitomi, Seiji, Ishibe, Youichi, Shimizu, Nobuyoshi
• Format: Journal Article
• Language: English
• Published: Japan 01.02.2006
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Apoptosis; Cell Line, Tumor; Cell Proliferation; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Esophageal Neoplasms - radiotherapy; Humans; Mitosis; Quinazolines - therapeutic use; Radiation Tolerance; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - metabolism; Signal Transduction - physiology
• ISSN: 0386-300X
• DOI: 10.18926/amo/30755

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 microM to 36.9 microM. 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.