Abstract
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.
Highlights
Lung cancer is the malignant tumour with the highest prevalence and mortality all over the world, accounting for 30%-40% in China and other developing countries.[1,2] According to pathological characteristics, lung cancer can be divided into non–small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC)
By using immunofluorescence staining and laser assay, we found that radiation induced GTSE1 nuclear translocation rapidly (Figure 4A); we surprisingly found that GTSE1 could be recruited to DSB site after radiation (Figure 4B), which means GTSE1 might participate in DNA damage repair directly after radiation
We utilized three different NSCLC cells to observe the role of GTSE1
Summary
Lung cancer is the malignant tumour with the highest prevalence and mortality all over the world, accounting for 30%-40% in China and other developing countries.[1,2] According to pathological characteristics, lung cancer can be divided into non–small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). A variety of comprehensive radiotherapy-based treatments have dominated the treatment of NSCLC, it cannot be avoided to overcome the growing radioresistance during radiotherapy.[7,8] The current research involving radiosensitization mainly falls into the following fields: tumour cell hypoxia tolerance, DNA damage repair, apoptosis, cell cycle disorders and antiangiogenic drugs, etc[912] most of these drugs are in the study process and cannot be applied to clinic for the normal tissue toxicity.[13]. We showed that GTSE1 could be recruited to DNA damage repair sites directly after irradiation. These data provide new idea to enhance radiosensitivity in non–small-cell lung cancer
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