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.