| Autor: |
Lin Li, Yuexian Li, Huawei Zou |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
PeerJ, Vol 9, p e12356 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2167-8359 |
| DOI: |
10.7717/peerj.12356 |
| Popis: |
Background Radioresistance is still the major cause of radiotherapy failure and poor prognosis in patients with non-small cell lung cancer (NSCLC). Apatinib (AP) is a highly selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2). Whether and how AP affects radiosensitivity in NSCLC remains unknown. The present study aimed to explore the radiosensitization effect of AP in NSCLC and its underlying mechanism as a radiosensitizer. Methods The NSCLC cell lines A549 and LK2 were treated with AP, ionizing radiation (IR), or both AP and IR. Expression of VEGFR2 was analyzed by western blot and RT-PCR. Cell proliferation was measured using CCK-8 and colony formation assays. Apoptosis and cell cycle distribution in NSCLC cells were analyzed by flow cytometry. Nuclear phosphorylated histone H2AX foci immunofluorescence staining was performed to evaluate the efficacy of the combination treatment. Western blot was used to explore the potential mechanisms of action. Results AP inhibited cell proliferation in a dose- and time-dependent manner. Flow cytometry analysis indicated that AP significantly increased radiation-induced apoptosis. Colony formation assays revealed that AP enhanced the radiosensitivity of NSCLC cells. AP strongly restored radiosensitivity by increasing IR-induced G2/M phase arrest. AP effectively inhibited repair of radiation-induced DNA double-strand breaks. Western blot analysis showed that AP enhanced radiosensitivity by downregulating AKT and extracellular signal-regulated kinase (ERK) signaling. Conclusion Our findings suggest that AP may enhance radiosensitivity in NSCLC cells by blocking AKT and ERK signaling. Therefore, AP may be a potential clinical radiotherapy synergist and a novel small-molecule radiosensitizer in NSCLC. Our study fills a gap in the field of anti-angiogenic drugs and radiosensitivity. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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