Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

Yu,Xiying; Fan,Hongjun; Jiang,Xingran; Zheng,Wei; Yang,Yanan; Jin,Mei; Ma,Xiaoli; Jiang,Wei

doi:10.3892/ol.2020.11913

Apatinib induces apoptosis and autophagy via the PI3K/AKT/mTOR and MAPK/ERK signaling pathways in neuroblastoma

Authors:
- Xiying Yu
- Hongjun Fan
- Xingran Jiang
- Wei Zheng
- Yanan Yang
- Mei Jin
- Xiaoli Ma
- Wei Jiang
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Affiliations: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Beijing Key Laboratory of Pediatric Hematology Oncology, National Discipline of Pediatrics, Ministry of Education, MOE Key Laboratory of Major Diseases in Children, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, P.R. China, Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, P.R. China
Published online on: July 27, 2020 https://doi.org/10.3892/ol.2020.11913
Article Number: 52
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The clinical outcome of neuroblastoma (NB) has significantly improved in the last 30 years for patients with localized disease; however, the overall survival (OS) for patients with metastasis remains poor. Apatinib, a selective inhibitor of the vascular endothelial growth factor receptor‑2 (VEGFR‑2) tyrosine kinase, which was discovered to be highly associated with metastasis, has been reported to exert antitumor effects in numerous types of cancer. However, the effect of apatinib in NB remains relatively unknown. The present study aimed to investigate the antitumor effects of apatinib in NB cells in vitro. The results revealed that apatinib inhibited cell viability and colony formation, whilst inducing cell cycle arrest and the apoptosis of NB cells. Additionally, apatinib inhibited the migration and invasion of NB cells, in addition to promoting the autophagy of NB cells. Western blotting demonstrated that the protein expression levels of phosphorylated (p)‑AKT, p‑mTOR and p‑P70S6K, and downstream molecules associated with the cell cycle and apoptosis, such as cyclin D1 and the Bcl‑2/Bax ratio of NB cells, were significantly decreased following treatment with apatinib. In addition, western blotting and immunofluorescence assays identified that the expression level of microtubule‑associated protein 1A/1B‑light chain 3‑II, which is expressed in autophagosomes, was upregulated following apatinib treatment. In conclusion, the findings of the present study suggested that apatinib may induce apoptosis and autophagy via the PI3K/AKT/mTOR and mitogen‑activated protein kinase/ERK signaling pathways in NB cells. Thus, apatinib may be a potential antitumor agent for the clinical treatment of NB.

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