Abstract：Objective To investigate the effect of epidermal growth factor receptor tyrosine kinase inhibitor on the radiosensitivity of human non-small cell lung cancer cells and its possible mechanism. Methods Human non-small cell lung cancer cells H1299 were cultured in vitro. CCK-8 was used to detect the toxic effects of erlotinib on H1299 cells, IC50 and IC20 were calculated, and IC20 was utilized as the drug concentration for subsequent experiments. The colony formation assay was performed to identifiy the effect of X-ray combined with erlotinib on H1299 cells,the radiosensitivity parameters were calculated, and the cell survival curves were delineated. Flow cytometry was conducted to detect the cell cycle distribution and apoptosis. Western blot analysis was used to detect the expression of EGFR/PI3K/AKT pathway and apoptosis-related proteins. Results Erlotinib exerted inhibitory effect upon the proliferation of H1299 cells, IC50 was calculated as 27.3μmol/L, and 3.3μmol/L for IC20. X-ray combined with IC20 concentration of erlotinib could reduce the cloning ability of H1299, increased the proportion of G0/G1 phase and G2/M phase, decreased the proportion of S phase, aggravated cell apoptosis, down-regulated the expression of pEGFR and pAKT proteins, and up-regulated the expression of apoptosis-related proteins including Active Caspase 3 and Cleaved PARP. Conclusions Erlotinib exerts a radiosensitizing effect on H1299. The possible mechanism is that erlotinib combined with radiation can suppress the EGFR/PI3K/AKT pathway, reduce the ability of repairing cell damage, change cell growth cycle and induce cell apoptosis.
Liu Dahai,Luo Jie,Liu Chunmei et al. Mechanism of radiosensitization of erlotinib to non-small cell lung cancer cell line H1299[J]. Chinese Journal of Radiation Oncology, 2020, 29(8): 682-686.
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