Department of Radiation Oncology, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
J Cell Mol Med. 2020 May;24(9):5162-5167. doi: 10.1111/jcmm.15165. Epub 2020 Mar 22.
Radiotherapy is an important strategy for NSCLC. However, although a variety of comprehensive radiotherapy-based treatments have dominated the treatment of NSCLC, it cannot be avoided to overcome the growing radioresistance during radiotherapy. The purpose of this study was to elucidate the radiosensitizing effects of NSCLC via knockdown GTSE1 expression and its mechanism. Experiments were performed by using multiple NSCLC cells such as A549, H460 and H1299. Firstly, we found GTSE1 conferred to radioresistance via clonogenic assay and apoptosis assay. Then, we detected the level of DNA damage through comet assay and γH2AX foci, which we could clearly observe knockdown GTSE1 enhance DNA damage after IR. Furthermore, through using laser assay and detecting DNA damage repair early protein expression, we found radiation could induce GTSE1 recruited to DSB site and initiate DNA damage response. Our finding demonstrated that knockdown GTSE1 enhances radiosensitivity in NSCLC through DNA damage repair pathway. This novel observation may have therapeutic implications to improve therapeutic efficacy of radiation.
放射治疗是 NSCLC 的重要策略。然而，尽管各种基于综合放射治疗的治疗方法已经主导了 NSCLC 的治疗，但在放射治疗过程中克服不断增长的放射抗性是不可避免的。本研究旨在通过敲低 GTSE1 表达来阐明 NSCLC 的放射增敏作用及其机制。实验通过使用多种 NSCLC 细胞（如 A549、H460 和 H1299）进行。首先，我们发现 GTSE1 通过集落形成实验和细胞凋亡实验赋予放射抗性。然后，我们通过彗星实验和 γH2AX 焦点检测来检测 DNA 损伤水平，我们可以清楚地观察到敲低 GTSE1 增强了 IR 后的 DNA 损伤。此外，通过使用激光实验和检测 DNA 损伤修复早期蛋白表达，我们发现辐射可以诱导 GTSE1 募集到 DSB 位点并启动 DNA 损伤反应。我们的发现表明，通过 DNA 损伤修复途径，敲低 GTSE1 可增强 NSCLC 的放射敏感性。这一新的观察结果可能具有治疗意义，可提高放射治疗的疗效。
