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Updated: Aug 11, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
09:04

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways

Qing Xu1, Jon Briggs, Sungman Park

  • 1H Lee Moffitt Cancer Center and Research Institute, Department of Interdisciplinary Oncology, University of South Florida College of Medicine, Tampa, FL 33612, USA.

Oncogene
|July 12, 2005
PubMed

Insights

Signal transducer and activator of transcription 3 (Stat3) is crucial for vascular endothelial growth factor (VEGF) expression in cancer. Inhibiting Stat3 effectively blocks tumor growth and angiogenesis by targeting HIF-1 and VEGF.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Vascular endothelial growth factor (VEGF) upregulation is common in cancer, driven by oncogenic proteins.
  • Hypoxia-inducible factor-1 (HIF-1) and Signal transducer and activator of transcription (Stat3) are key transcription activators of VEGF.
  • Both HIF-1 and Stat3 are frequently upregulated in various cancers, presenting a complex therapeutic challenge.

Purpose of the Study:

  • To investigate the role of Stat3 in regulating HIF-1 and VEGF expression in cancer.
  • To determine if Stat3 is a viable therapeutic target for inhibiting tumor growth and angiogenesis.

Main Methods:

  • Investigated Stat3's requirement for basal and growth signal-induced HIF-1 expression.
  • Assessed the impact of Stat3 inhibition on VEGF induction by oncogenic stimuli (IL-6R, c-Src, Her2/Neu).
  • Utilized small-molecule Stat3 inhibitors in vitro and in vivo tumor models.

Main Results:

  • Stat3 is essential for both basal and growth signal-induced HIF-1 expression.
  • Stat3 inhibition attenuated VEGF induction by diverse oncogenic stimuli.
  • Targeting Stat3 with a small-molecule inhibitor suppressed HIF-1 and VEGF expression, inhibited tumor growth, and reduced angiogenesis in vivo.
  • Stat3 inhibition abrogated IL-6R-induced angiogenic capacity in tumor cells.

Conclusions:

  • Stat3 is a critical regulator of HIF-1 and VEGF expression in cancer.
  • Stat3 is a promising therapeutic target for inhibiting tumor angiogenesis and growth.
  • Targeting Stat3 offers a strategy to overcome the complexity of VEGF upregulation in cancer.

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