Proteomics of the radioresistant phenotype in H1299 cells: SLC2A1 as a radiosensitivity marker

Abstract

\n Background: Radiotherapy is a main method for the treatment of malignant tumors. However, radiation resistance of tumor cells is the main reason for poor prognosis. The purpose of this study was to screen the differentially expressed protein (DEP), and its key protein related to radiation resistance in photon-resistant lung adenocarcinoma cell line H1299. Methods: In this study, we investigated the cell viability and colony formation were examined to evaluate the potent proliferation-inhibiting effect of photo therapy on the H1299 cells. Flow cytometry was used to detect apoptosis. Further we selected the appropriate irradiation dose after photon irradiation of radioresistant cell H1299 for screening and validation of radioresistance-related DEPs by proteomic analysis. Furthermore, we also studied the SLC2A1 and irradiation sensitivity potential. Results: The results showed a dose‑dependent decrease of viable cell percentage following high dose of exposure (at dose of 8 and 10 Gy), and a prolonged the prolongation of H1299 cell cycle arrest, induced apoptosis. Proteomic analysis using iTRAQ revealed a total of 46 DEPs were identified including 30 up-regulated and 16 down-regulated DEPs in inhibition. Western blotting validated the respective changes in protein expression. DEPs were significantly associated with five-year survival in patients with lung adenocarcinoma. In addition, after knocking down SLC2A1, it was found that 4Gy radiation could significantly inhibit the proliferation of H1299 cells and regulate G2 phase arrest of cell cycle by down-regulating Cdk2. Conclusions: These findings suggest the ITGA6,EIF4G1 and SLC2A1 protein is closely related to radiation resistance of lung adenocarcinoma, and SLC2A1 expression is significantly related to patient survival, so it can increase the sensitivity of H1299 cells to photon rays.