EXPRESSIONS OF HYPOXIA-INDUCIBLE FACTOR-1 alpha, VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTORS IN BOVINE ENDOMETRIUM THROUGHOUT THE ESTROUS CYCLE

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.

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Effect of tetrandrine on the expressions of hypoxia-inducible factor-1 and vascular endothelial growth factor in neovascularized cornea

African Journal of Pharmacy and Pharmacology ◽

10.5897/ajpp11.265 ◽

2011 ◽

Vol 5 (9) ◽

pp. 1223-1227 ◽

Cited By ~ 1

Author(s):

Guangli Sun

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Hypoxia Inducible Factor ◽

Vascular Endothelial ◽

Hypoxia Inducible Factor 1 ◽

Endothelial Growth Factor

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Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide

Blood ◽

10.1182/blood.v95.1.189 ◽

2000 ◽

Vol 95 (1) ◽

pp. 189-197 ◽

Cited By ~ 292

Author(s):

Hideo Kimura ◽

Alessandro Weisz ◽

Yukiko Kurashima ◽

Kouichi Hashimoto ◽

Tsutomu Ogura ◽

...

Keyword(s):

Nitric Oxide ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Hypoxia Inducible Factor ◽

Vascular Endothelial ◽

Hypoxia Response Element ◽

Response Element ◽

Hypoxia Response ◽

Hypoxia Inducible Factor 1 ◽

Endothelial Growth Factor

Abstract Nitric oxide (NO) regulates production of vascular endothelial growth factor (VEGF) by normal and transformed cells. We demonstrate that NO donors may up-regulate the activity of the human VEGF promoter in normoxic human glioblastoma and hepatoma cells independent of a cyclic guanosine monophosphate–mediated pathway. Deletion and mutation analysis of the VEGF promoter indicates that the NO-responsive cis-elements are the hypoxia-inducible factor-1 (HIF-1) binding site and an adjacent ancillary sequence that is located immediately downstream within the hypoxia-response element (HRE). This work demonstrates that the HRE of this promoter is the primary target of NO. In addition, VEGF gene regulation by NO, as well as by hypoxia, is potentiated by the AP-1 element of the gene. Our study also reveals that NO and hypoxia induce an increase in HIF-1 binding activity and HIF-1 protein levels, both in the nucleus and the whole cell. These results suggest that there are common features of the NO and hypoxic pathways of VEGF induction, while in part, NO mediates gene transcription by a mechanism distinct from hypoxia. This is demonstrated by a difference in sensitivity to guanylate cyclase inhibitors and a different pattern of HIF-1 binding. These results show that there is a primary role for NO in the control of VEGF synthesis and in cell adaptations to hypoxia. (Blood. 2000;95:189-197)

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