ArticleCell death & disease2017
Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
165 citing papers in PubMed, 2 syntheses or guidelines pooled it, 266 citations in OpenAlex.
- Efficacy and safety of apatinib in the treatment of osteosarcoma: a single-arm meta-analysis among Chinese patients.BMC cancer · 2021Pooled it
- Assessment of Efficiency and Safety of Apatinib in Advanced Bone and Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy.Cancer biology & medicine · 2020Trial
- A randomized phase 2 trial of apatinib vs observation as maintenance treatment following first-line induction chemotherapy in extensive- stage small cell lung cancer.Investigational new drugs · 2020Trial
- Apatinib Mesylate in the treatment of advanced progressed lung adenocarcinoma patients with EGFR-TKI resistance -A Multicenter Randomized Trial.Scientific reports · 2019Trial
- Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial.The oncologist · 2019Trial
- Apatinib inhibits synovial sarcoma progression and angiogenesis via VEGFR2-mediated AKT/FOXO3A and ERK1/2/FOXM1 signaling pathways.Cell death discovery · 2026Article
- THOC3 interacts with epithelial-to-mesenchymal transition to promote non-small cell lung cancer carcinoma progression through STAT3 signaling pathway.Translational oncology · 2026Article
- Alterations of the tumor microenvironment (TME) by exploratory gene expression analysis in recurrent glioblastoma following apatinib in combination with temozolomide.Biochemistry and biophysics reports · 2026Article
- Microbiota in cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Synergistic Anticancer Effects of Apatinib and PD-L1 Inhibition in Breast Cancer.Journal of mammary gland biology and neoplasia · 2026Article
- The Heterogeneity and Function of Stromal Cells in the Tumor Microenvironment.Research (Washington, D.C.) · 2026Review
- Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (Review).Oncology letters · 2026Review
- The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.Journal of bone oncology · 2025Review
- Bibliometric analysis of autophagy in the diagnosis and treatment of osteosarcoma: a bibliometric analysis (2007-2023).Cancer biology & therapy · 2025Article
- Cholesterol confers resistance to Apatinib-mediated ferroptosis in gastric cancer.Cell & bioscience · 2025Article
- KRAS regulates IL-17 signal activity by affect the metastasis of osteosarcoma via an IL-17A-dependent manner.JBMR plus · 2025Article
- Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma.Genes & diseases · 2025Review
- D-mannose suppresses the angiogenesis and progression of colorectal cancer.Acta biochimica et biophysica Sinica · 2025Article
- Advancements in Osteosarcoma Therapy: Overcoming Chemotherapy Resistance and Exploring Novel Pharmacological Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
105 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cure rate of osteosarcoma has not improved in the past 30 years. The search for new treatments and drugs is urgently needed. Apatinib is a high selectivity inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine kinase, exerting promising antitumoral effect in various tumors. The antitumor effect of Apatinib in human osteosarcoma has never been reported. We investigated the effects of Apatinib in osteosarcoma in vitro and in vivo. Osteosarcoma patients with high levels of VEGFR2 have poor prognosis. Apatinib can inhibit cell growth of osteosarcoma cells. In addition to cycle arrest and apoptosis, Apatinib induces autophagy. Interestingly, inhibition of autophagy increased Apatinib-induced apoptosis in osteosarcoma cells. Immunoprecipitation confirmed direct binding between VEGFR2 and signal transducer and activator of transcription 3 (STAT3). Downregulation of VEGFR2 by siRNA resulted in STAT3 inhibition in KHOS cells. VEGFR2 and STAT3 are inhibited by Apatinib in KHOS cells, and STAT3 act downstream of VEGFR2. STAT3 and BCL-2 were downregulated by Apatinib. STAT3 knockdown by siRNA reinforced autophagy and apoptosis induced by Apatinib. BCL-2 inhibits autophagy and was apoptosis restrained by Apatinib too. Overexpression of BCL-2 decreased Apatinib-induced apoptosis and autophagy. Apatinib repressed the expression of STAT3 and BCL-2 and suppressed the growth of osteosarcoma in vivo. To sum up, deactivation of VEGFR2/STAT3/BCL-2 signal pathway leads to Apatinib-induced growth inhibition of osteosarcoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.