These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway.
    Author: Zhong XS, Zheng JZ, Reed E, Jiang BH.
    Journal: Biochem Biophys Res Commun; 2004 Nov 12; 324(2):471-80. PubMed ID: 15474452.
    Abstract:
    Ovarian cancer has the highest mortality rate of any gynecological disease affecting women in Western countries. VEGF is a crucial inducer of angiogenesis both in vivo and in vitro. VEGF is commonly upregulated in ovarian cancer and is regulated by HIF-1. SU5416 is known to inhibit various stages of tumor growth. In this study, we show that SU5416 inhibited VEGF mRNA expression in ovarian cancer cells in a dose-dependent manner. SU5416 inhibited VEGF expression at the transcriptional level through the HIF-1 DNA binding site. HIF-1 is composed of HIF-1alpha and HIF-1beta subunits. SU5416 specifically decreased HIF-1alpha, but not HIF-1beta protein levels. To understand the signaling pathways regulating SU5416-inhibited VEGF and HIF-1alpha expression, we found that SU5416 inhibited PI3K activity. AKT is a downstream target of PI3K. We found that SU5416 also inhibited AKT and p70S6K1 activation and activity in a dose-dependent manner. These results demonstrate that SU5416 inhibited VEGF and HIF-1alpha expression through the inhibition of PI3K/AKT/p70S6K1 pathway in ovarian cancer cells. These results indicate that SU5416 may be an effective agent for ovarian cancer treatment through the inhibition of VEGF and HIF-1 expression, and the activation of PI3K/AKT/p70S6K1 signaling pathway.
    [Abstract] [Full Text] [Related] [New Search]