Conclusion
Taken together, our study demonstrates that EGFR mutations are closely associated with the increased sensitivity of NSCLC cell lines to X-ray irradiation and that EGFR mutation status is a potentially useful indicator to evaluate the effectiveness of radiotherapy in the treatment of NSCLC.
Methods
Eight NSCLC cell lines with different EGFR gene status were irradiated by linear accelerator, and the radiosensitivity between the cell lines was compared by cell colony formation assay and cell proliferation assay. Cell cycle and apoptosis were analysed by flow cytometry. Radiosensitivity-related protein expression was detected by Western blotting.
Results
In the present study, we found that NSCLC cell lines with the epidermal growth factor receptor (EGFR) gene mutations were more sensitive to X-ray irradiation than those with wild-type EGFR (P<0.05). No difference in radiosensitivity was observed between NSCLC cells with EGFR exon19 deletion (Del 19) mutation and exon 21 point mutation at position 858 (L858R) with or without T790M mutation (P<0.05), as well as between NSCLC cells with EGFR mutation and those with acquired EGFR-tyrosine kinase inhibitors (TKIs) resistance. Mechanistically, EGFR mutations promoted NSCLC cell apoptosis in response to X-ray irradiation through the upregulation of proapoptotic protein Bax and downregulation of anti-apoptotic proteins such as Bcl-2 and DNA-dependent protein kinase catalytic subunit. In addition, phosphorylated histone (γ-H2AX) foci assay showed that EGFR mutations sustained irradiation-induced DNA damage.