Increased Radioresistance of Human Non-Small Cell Lung Cancer Cells Surviving Cisplatin Exposure

Purpose: To evaluate radioresistance of human non-small cell lung cancer (NSCLC) cells that survived and showed sustained growth after exposure to cisplatin. Material and methods: The work used the NSCLC cell line A549, which was exposed to cisplatin at a concentration of 2.5 μg/ml four times to obtain a cell population that survives and produces stable growth after exposure to cisplatin, A549Pt. Cell irradiation was carried out on a RUB RUST-M1 X-ray biological installation (Russia) at a dose rate of 0.85 Gy/min. Cell death was assessed using flow cytometry. To analyze the effectiveness of DNA repair from double-strand breaks (DSBs), we used a quantitative assessment of the foci of DNA DSB marker proteins γH2AX and 53BP1. Results: A549Pt NSCLC cells that survived and grew robustly after exposure to cisplatin exhibited reduced activation of apoptosis and produced less 53BP1 in response to additional cisplatin exposure compared to parental A549 cells. A549Pt also exhibit resistance to X-ray radiation, manifested in a decrease in the quantitative yield of foci of DNA DSB marker proteins γH2AX and 53BP1. The resistance of A549Pt cells to the effects of ionizing radiation, revealed in this work, can significantly reduce the effectiveness of neoadjuvant chemoradiation therapy for malignant neoplasms. Further research is needed to identify the detailed cellular and molecular mechanisms of the resistance of surviving cells to radiation therapy acquired during chemotherapy. In the future, this will increase the effectiveness of treatment of malignant neoplasms and avoid relapses.