Author:
Chen Li,Lin Guoxiang,Chen Kaihua,Wan Fangzhu,Liang Renba,Sun Yongchu,Chen Xishan,Zhu Xiaodong
Abstract
AbstractVascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. VEGF was reported to promote the occurrence of autophagy, which enhanced the radioresistance of tumors. The purpose of this study was to investigate the influence of VEGF silencing on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells and the underlying mechanisms. The radiosensitivity of NPC cells after VEGF silencing was detected by cell counting kit 8 (CCK-8) and clonogenic assay, while cell cycle and apoptosis were detected by flow cytometry. The processes of DNA damage, repair and autophagy were examined by immunofluorescence and western blotting. The interaction between VEGF and mTOR was confirmed by western blotting and co-immunoprecipitation studies. The effect of VEGF on radiosensitivity of NPC cells was investigated in vivo using a xenograft model. Furthermore, immunohistochemistry and TUNEL assays were used to verify the relationship between autophagy and radiosensitivity in NPC after VEGF depletion. Downregulation of VEGF significantly inhibited cell proliferation and induced apoptosis of NPC cells after radiotherapy in vitro and in vivo. In addition, VEGF knockdown not only decreased autophagy level, but also delayed the DNA damage repair in NPC cells after irradiation. Mechanistically, silencing VEGF suppressed autophagy through activation of the mTOR pathway. VEGF depletion increased radiosensitivity of NPC cells by suppressing autophagy via activation of the mTOR pathway.
Funder
National Natural Science Foundation of China
Youth Science Foundation of Guangxi Medical University
Middle-aged and Young Teachers’ Basic Ability Promotion Project of Guangxi
Publisher
Springer Science and Business Media LLC
Reference52 articles.
1. Cao, S. M., Simons, M. J. & Qian, C. N. The prevalence and prevention of nasopharyngeal carcinoma in China. Chin. J. Cancer 30, 114–119 (2011).
2. Feng, X. P. et al. Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Can. Res. 70, 3450–3462 (2010).
3. Cohen-Jonathan Moyal, E. Angiogenic inhibitors and radiotherapy: From the concept to the clinical trial. Cancer Radiother. 13, 562–567 (2009).
4. Hu, L. et al. Apatinib enhances the radiosensitivity of the esophageal cancer cell line KYSE-150 by inducing apoptosis and cell cycle redistribution. Oncol. Lett. 17, 1609–1616 (2019).
5. Yu, L., Chen, Y. & Tooze, S. A. Autophagy pathway: Cellular and molecular mechanisms. Autophagy 14, 207–215 (2018).
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