Effects of valproic acid on proliferation, apoptosis, angiogenesis and metastasis of ovarian cancer in vitro and in vivo.

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.