Interaction of Radiation and Gefitinib on a Human Lung Cancer Cell Line with Mutant EGFR Gene In Vitro

Aim: To investigate the effect of gefitinib in combination with irradiation using HCC827 cells, a human lung cancer cell line bearing epidermal growth factor receptor (EGFR) mutation. Materials and Methods: The effects of treatment with radiation with and without gefitinib on HCC27 cells were assessed using a clonogenic assay. Apoptosis was measured by flow cytometry and EGFR signal transduction was evaluated by western blotting. Results: The Dq - quasi-threshold dose, the dose at which the straight portion of the survival curve, extrapolated backward, cuts the dose axis drawn through a survival fraction of unity after radiation-alone and after combination treatment were 0.41 +/- 0.09 Gy and 0.08 +/- 0.11 Gy, respectively; thus indicating that combination treatment resulted in supra-additive effects of radiation. There was no significant difference on the D0 - final slope of the survival curve (the dose required to reduce the fraction of surviving cells to 37% of its previous value) between-radiation alone and the combination treatment. Apoptosis significantly increased after the combination treatment in comparison to what was observed after radiation-alone. The expression of phosphorylated EGFR (pEGFR), phosphorylated ERK1/2 (pERK1/2) and phosphorylated AKT (pAKT) after the combination decreased in comparison to what was observed after radiation-alone. Conclusion: Gefitinib enhances radiosensitivity of supra-additively HCC827 cells by inhibiting the activation of the anti-apoptotic and proliferative signal transduction pathways.