nhibition of HIF-1α and VEGF was significantly reversed by forced expression of the mAKT protein, and the higher the expression of mAKT, the higher the expression of the HIF-1α reporter and VEGF reporter. These results demonstrate that GA inhibits HIF-1α and VEGF expression through blocking the phosphorylation of AKT. The regulating effect of AKT on HIF-1α or VEGF expression in ovarian cancer cells was also reported ([@b35-or-35-01-0291],[@b36-or-35-01-0291]). Research into how the PI3K/AKT/mTOR pathway affects the progression and tumorigenesis of ovarian cancer may lead to new therapies that will increase the survival of these patients ([@b37-or-35-01-0291]). The inhibitory effect of GA on the PI3K/Akt pathway demonstrates great therapeutic potential for ovarian cancer.

GA upregulates PTEN expression in OVCAR-3 ovarian cancer cells
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Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor commonly mutated in many human cancers. PTEN hydrolyzes the 3-phosphate on PIP3 to generate PIP2 and negatively regulates PIP3-mediated signaling pathways. AKT is one of the most important downstream targets of PI3K. Therefore, PTEN can control HIF-1α and VEGF expression through the PI3K/AKT pathway ([@b38-or-35-01-0291]). To examine whether PTEN is involved in the inhibition of HIF-1α and VEGF expression by GA, the level of PTEN protein was investigated by western blot analysis. As shown in [Fig. 5](#f5-or-35-01-0291){ref-type="fig"}, the protein levels of PTEN in the OVCAR-3 cancer cell line were increased following treatment with a high concentration of GA. This increase in PTEN protein expression indicates that GA may inhibit HIF-1α and VEGF expression through upregulating PTEN protein.

In conclusion, we investigated the molecular mechanism of GA concerning its inhibition of VEGF expression and *in vitro* angiogenesis activity. In the present study, GA was found to directly inhibit VEGF secretion of ovarian cancer cells at ph