Radiation dose effect on non-small cell lung cancer based on driver genotyping: An exploratory study / 肿瘤

ABSTRACT

Objective: To explore the importance of distinguishing α/β values for different lung cancer cells based on driver genes and its significance in the precise radiotherapy. At the same time, to study the influence of serine/threonine kinase inhibitor MK1775 on the α/β values for different kinds of cells, and to investigate the radiation sensitization or synergistic effect of MK1775. Methods: Lung cancer PC9 cells with epidermal growth factor receptor (EGFR) gene mutant, A549 cells with V-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog (K-RAS) gene mutant, and H1299 cells with p53 gene mutant were respectively cultured and assigned into three groups the control group, radiation alone group, and MK1775 inhibitor combined with radiation group. 6 MV X-ray with a dose rate of 3 Gy/min was employed in all the radiation groups, in which the administered dosages were 0, 0.25, 0.5, 1, 2, 3, 4, 5 and 6 Gy, respectively. Finally, the dose-effect relationship was analyzed by employing clone counting method, and the radiosensitization and synergistic effects of MK1775 on the three kinds of gene mutant cells were analyzed. Results: The different gene mutation types corresponded to different hyper-radiosensitivity doses. The numbers of PC9, A549 and H1299 cell clones were decreased to 56.4%, 54.5% and 73.2% respectively after adding MK1775 inhibitor, which indicated that the synergy effect exists indeed between MK1775 and radiation. The α/β values were negative in PC9 and H1299 cells (except of A549 cells) before MK1775 treatment, and all the α/β values in PC9, H1299 and A549 cells in MK1775 combined with radiation group were positive. So it was indicated that the radiosensitizing effect of MK1775 inhibitor only worked when α/β value was negative. Additionally, there was significant difference between the radiation alone group and MK1775 combined with radiation group (P < 0.05). Conclusion: The different driver genes correspond to different α and β values, thus correspond to different equivalent biological doses. Simultaneously, MK1775 maybe have the different radiosensitization or radiosynergistic effect for lung cancer cells with different driver genotypes.