Inhibitory effect of valproic acid on human ovarian cancer in nude mice

Objective:To investigate the effect of valproic acid(VPA) and of VPA combining with diamminedichloroplatinum(DDP) on the growth of human ovarian cancer in nude mice.Methods: A human ovarian cancer model subcutaneously transplanted into nude mice was established.They were divided into 4 groups: the VPA group,the DDP group,the VPA+DDP group and the control group,6 in each.Tumor volume and weight were determined.Flowcytometry(FCM) was used to assess the characters of apoptosis in the tissues of tumor,liver and brain.The protein level of the vascular endothelial growth factor(VEGF) was also determined by FCM.Results: The inhibitory rate in the VPA,DDP,and VPA+DDP groups was as follows:40.7%,45.3%,and 58.0%,which was significantly higher than that in the control group(P0.01).The apoptotic rate in the VPA,DDP,and VPA+DDP groups was as follows:(27.05±1.63)%,(35.93±3.89)%,and(42.59±2.55)%,which was significantly higher than that in the control group(16.73±2.82)%(P0.01).The cell cycle distribution changed in VPA,DDP,and VPA+DDP groups,and cells in the S-phase significantly decreased.There were no significant apoptosis in liver tissues and brain tissues in any of the groups.The VEGF protein level in the VPA,DDP,and VPA+DDP groups was lower than that in the control group.Conclusions: VPA can inhibit the growth of ovarian cancer by inducing the apoptosis of tumor cells and inhibiting the angiogenesis of human ovarian cancer subcutaneously transplanted into nude mice,furthermore its combination with DDP can enhance the anticancer effects with a minimal side effect profile.