VEGF knockdown enhances radiosensitivity of nasopharyngeal carcinoma by inhibiting autophagy through the activation of mTOR pathway
| العنوان: | VEGF knockdown enhances radiosensitivity of nasopharyngeal carcinoma by inhibiting autophagy through the activation of mTOR pathway |
|---|---|
| المؤلفون: | Yongchu Sun, Renba Liang, Xiao-Dong Zhu, Li Chen, Fangzhu Wan, Xishan Chen, Kai-Hua Chen, Guoxiang Lin |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-14 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Vascular Endothelial Growth Factor A, Molecular biology, Mice, Nude, lcsh:Medicine, Radiation Tolerance, Article, chemistry.chemical_compound, Mice, Radioresistance, Cell Line, Tumor, medicine, Autophagy, otorhinolaryngologic diseases, Animals, Humans, Radiosensitivity, lcsh:Science, PI3K/AKT/mTOR pathway, Cancer, Mice, Inbred BALB C, Multidisciplinary, Nasopharyngeal Carcinoma, Cell growth, TOR Serine-Threonine Kinases, lcsh:R, Nasopharyngeal Neoplasms, Cell cycle, medicine.disease, Vascular endothelial growth factor, stomatognathic diseases, Nasopharyngeal carcinoma, chemistry, Oncology, Gene Knockdown Techniques, Cancer research, lcsh:Q, Neoplasm Transplantation |
| الوصف: | Vascular 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d031c442749b0143cea09f4e07cd7e13 http://link.springer.com/article/10.1038/s41598-020-73310-x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d031c442749b0143cea09f4e07cd7e13 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
|---|