Effects of Valproic Acid on Proliferation, Apoptosis, Angiogenesis and Metastasis of Ovarian Cancer in Vitro and in Vivo

Abstract

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