TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000672860
  • Gene Name:VEGF
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:Northern blot
  • mRNA Pathway:VEGF signaling pathway
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB06436
  • Drug Name:Semaxanib(SU5416)
  • Drug Method:down-regulated the gene expression the gene expression

Disease basic infommation

  • Disease:ovarian cancer
  • Tissue:cell lines (OVCAR-3,A2780/CP70)

Other information

  • Title:SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway
  • Journal:Biochem Biophys Res Commun
  • Published:2004
  • 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.
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