Mechanism of radiosensitization of erlotinib to non-small cell lung cancer cell line H1299 / 中华放射肿瘤学杂志

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, IC 50 and IC 20 were calculated, and IC 20 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, IC 50 was calculated as 27.3 μmol/L, and 3.3 μmol/L for IC 20. X-ray combined with IC 20 concentration of erlotinib could reduce the cloning ability of H1299, increased the proportion of G 0/G 1 phase and G 2/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.