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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.
- Source :
-
Pharmacology [Pharmacology] 2021; Vol. 106 (9-10), pp. 509-519. Date of Electronic Publication: 2021 Aug 19. - Publication Year :
- 2021
-
Abstract
- 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.<br />Objective: The study aimed to investigate the role of apatinib that targets vascular endothelial growth factor receptor-2 (VEGFR2) in ICC.<br />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.<br />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.<br />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.<br /> (© 2021 S. Karger AG, Basel.)
- Subjects :
- Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Humans
Hypoxia-Inducible Factor 1 drug effects
Signal Transduction drug effects
Transcription Factor 3 drug effects
Vascular Endothelial Growth Factor Receptor-2 drug effects
Antineoplastic Agents pharmacology
Bile Duct Neoplasms pathology
Cholangiocarcinoma pathology
Neovascularization, Pathologic pathology
Pyridines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0313
- Volume :
- 106
- Issue :
- 9-10
- Database :
- MEDLINE
- Journal :
- Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34412054
- Full Text :
- https://doi.org/10.1159/000514410