Icotinib Enhanced Radiosensitization of Nasopharyngeal Carcinoma by Inhibiting the Expression of Epidermal Growth Factor Receptor

Epidermal growth factor receptor (EGFR) is frequently overexpressed in multiple malignancies. Icotinib (IH), anew EGFR tyrosine kinase inhibitor, enhances radiosensitivity in various types of cancer, but its effect on nasopharyngeal carcinoma (NPC) remains unclear. Total 115 NPC tissue sections and 30 nasopharyngitis tissue sections were enrolled. The correlation of EGFR expression and clinicopathologic features of NPC was analyzed.Survival analysis was calculated by using univariate and multivariate regression analysis. A radioresistant NPCcell line, CNE-2R, was established with a gradient irradiation schedule. Cell viability, colony formation and EGFRexpression of CNE-2/2R cells were examined. Significant higher expression of EGFR was observed in NPC tissuesthan chronic nasopharyngitis lesions. EGFR expression was significantly correlated with both tumor stage(P < 0.001) and tumor-node-metastasis stage of NPC (P = 0.006). EGFR expression was an independent prognostic factor of disease-free survival (P = 0.047) and the overall survival of NPC (P = 0.016). Cell viability was higherin CNE-2R than CNE-2 on days 1, 2, 4, and 6 after radiation of 4 Gy. The colony number of CNE-2R was significantly higher than that of CNE-2 (P < 0.05), while IH enhanced the radiosensitizing effect of CNE-2R withlower survival fraction (P < 0.05). EGFR mRNA and protein expression levels were significantly higher inCNE-2R cells compared to CNE-2 cells, but significantly decreased after IH treatment (all P < 0.05). In conclusion, high EGFR expression is a poor prognostic factor for NPC patients. IH enhances the radiosensitivity ofCNE-2R cells and reduce EGFR expression.