The drug-resistance to gefitinib in PTEN low expression cancer cells is reversed by irradiation in vitro

To investigate the drug-resistance reversal to gefitinb and the mechanism in PTEN low expression cells which radiated with X-rays in vitro, We demonstrated that H-157 lung cancer cells (low-expression of PTEN but phospho-EGFR overexpressed tumor cells) exposed to X-rays. The PTEN expressions and radiosensitizing effects of tyrosine kinase inhibitor before and after irradiation were observed. The cell-survival rates were evaluated by colony-forming assays. The cell apoptosis was investigated using FCM. The expressions of phospho-EGFR and PTEN were determined by Western blot analysis.The results showed that the PTEN expressions were significantly enhanced by X-rays. Moreover, the cell growth curve and survival curve were down-regulated in the gefitinib-treated groups after irradiation. Meanwhile, the radiation-induced apoptosis of tumor cells was increased by inhibition of the EGFR through up-regulation of PTEN.These results suggested that PTEN gene is an important regulator on TKI inhibition, and the resistance to tyrosine kinase inhibitors might be reversed by irradiation in PTEN low expression cancer cells.The EGFR is a receptor tyrosine kinase that regulates fundamental processes of cell growth and differentiation. Overexpression of EGFR and its ligands, were reported for various epithelial tumors in the 1980s [1,2] and generated interest in EGFR as a potential target for cancer therapy [3-9]. These efforts have been rewarded in recent years as ATP site-directed EGFR tyrosine kinase inhibitors has shown anti-tumor activity in subsets of patients with non-small cell lung cancer [10,11], squamous cell carcinomas of the head and neck [12], and selected other malignancies [13-17]. The current data from retrospectively analyzed clinical trials and preclinical models [18-23] suggested that monotherapy with EGFR kinase inhibitors is unlikely to be effective in PTEN-deficient tumors, even if they harbor activating EGFR mutations. This could potentially result in upfront r