Proton Irradiation Sensitizes Radioresistant Non-small Cell Lung Cancer Cells by Modulating Epidermal Growth Factor Receptor-mediated DNA Repair

Abstract

Although proton radiotherapy is effective in treating various types of cancer, little is known on the biological responses triggered by proton irradiation. In the present study, we investigated protein profiles following proton irradiation of non-small cell lung cancer (NSCLC) cells and defined the role of proton-induced epidermal growth factor receptor (EGFR) expression in NSCLC cells. We found that proton irradiation more effectively sensitized NSCLC cells than gamma irradiation did. The expression profiles of radiosensitive and radioresistant NSCLC cells following proton and gamma irradiation were examined using antibody arrays. With regard to proteins, expression of EGFR was the most highly induced by proton irradiation. In addition, we found that EGFR inhibition with gefinitib significantly increased the radiosensitivity of NSCLC cells, and that increased radiosensitivity due to gefinitib was mediated by the suppression of DNA repair in radioresistant NSCLC cells. Thus, our data provide the first evidence that proton irradiation sensitizes radioresistant NSCLC cancer cells by modulating EGFR-mediated DNA repair.

Keywords: DNA repair; EGFR; gamma radiation; lung cancer; proton radiation.