Apatinib Inhibits Angiogenesis in Intrahepatic Cholangiocarcinoma by Regulating the Vascular Endothelial Growth Factor Receptor-2/Signal Transducer and Activator of Transcription Factor 3/Hypoxia Inducible Factor 1 Subunit Alpha Signaling Axis
| Autor: | Shan-Zhi Gu, Manping Huang, Zheng-Ping Xiong, Tian Tang, Guowen Li, Sai-Nan Zeng, Bin Huang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pyridines
Angiogenesis Antineoplastic Agents Cholangiocarcinoma Transcription Factor 3 chemistry.chemical_compound Cell Line Tumor Humans Apatinib STAT3 Cell Proliferation Pharmacology Tube formation Dose-Response Relationship Drug Neovascularization Pathologic biology Cell growth Kinase insert domain receptor General Medicine Vascular Endothelial Growth Factor Receptor-2 Vascular endothelial growth factor Bile Duct Neoplasms chemistry biology.protein Cancer research STAT protein Hypoxia-Inducible Factor 1 Signal Transduction |
| Zdroj: | Pharmacology. 106:509-519 |
| ISSN: | 1423-0313 0031-7012 |
| DOI: | 10.1159/000514410 |
| Popis: | Introduction: Intrahepatic cholangiocarcinoma (ICC), which is difficult to diagnose and is usually fatal due to its late clinical presentation and a lack of effective treatment, has risen over the past decades but without much improvement in prognosis. Objective: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC. Methods: MTT assays, cell scratch assays, and tube formation assays were used to assess the effect of apatinib on human ICC cell line (HuCCT-1) and RBE cells proliferation, migration, and angiogenic capacity, respectively. Expression of vascular endothelial growth factor (VEGF), VEGFR2, signal transducer and activator of transcription factor 3 (STAT3), pSTAT3, and hypoxia inducible factor 1 subunit alpha (HIF-1α) pathway proteins was assessed using Western blotting and mRNA expression analysis in HuCCT-1 was performed using RT-qPCR assays. The pcDNA 3.1(-)-VEGFR2 and pcDNA 3.1(-)-HIF-1α were transfected into HuCCT-1 and RBE cells using Lipofectamine 2,000 to obtain overexpressed HuCCT-1 and RBE cells. Results: We found that apatinib-inhibited proliferation, migration, and angiogenesis of HuCCT-1 and RBE cells in vitro in a dose-dependent manner. We also proved that apatinib effectively inhibits angiogenesis in tumor cells by blocking the expression of VEGF and VEGFR2 in these cells. In addition, we demonstrated that apatinib regulates the expression of STAT3 phosphorylation by inhibiting VEGFR2. Finally, we showed that apatinib regulates ICC angiogenesis and HIF-1α/VEGF expression via STAT3. Conclusions: Based on the above findings, we conclude that apatinib inhibits HuCCT-1 and RBE cell proliferation, migration, and tumor angiogenesis by inhibiting the VEGFR2/STAT3/HIF-1α axis signaling pathway. Apatinib can be a promising drug for ICC-targeted molecular therapy. |
| Databáze: | OpenAIRE |
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