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 HCC827 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.