Study On The Inhibitory Effects Of VPA On Human Ovarian Cancer Cell Line SKOV3 In Nude Mice

Objective:To investigate the effect of valproic acid(VPA)used alone and in combination with Diamminedichloroplatinum(DDP)on the growth of human ovarian cancer transplanted subcutaneously in nude mice.Methods:Human ovarian cancer model transplanted subcutaneously in nude mice was established,and divided into 4 groups:control group,VPA group,DDP group and VPA+DDP group.Tumor volume and weight were detected. Flowcytometry(FCM)was used to assessed the characters of apoptosis in the tissues of tumor,liver and brian.The protein levels of c-myc,CA-125 and hTERT were determined by Flowcytometry.Results:(1)In subcutaneous tumor model the dimension of the tumor in experimental group is smaller than that of the control group.The longer VPA being used the smaller the tumors were.The inhibiting rate of VPA group,DDP group and VPA+DDP group were as follows:40.7%,45.3%,58%,they were significantly higher than control group(P＜0.01).(2)Under light,a number of characteristic apoptotic cells were found in tumors of experimental groups.However,in the control groups there were few.The apoptotic rate of experimental groups were as follows:(27.05±1.63)%,(35.93±3.89)%,(42.59±2.55)%,which were significantly higher than control group (16.73±2.82)%(P＜0.01).The cell cycle distribution changed in experimental group,the S-phase was decrease.(3)There were no toxic reactions during the course.The apoptotic rates of the liver and brain tissues in nude mice were very low(P＞0.05).(4)The result of FCM indicated that after using VPA,the expression of c-myc, CA-125 and hTERT were decreased,and there was a significant difference among each group(P＜0.05).Conclusions:(1)VPA can significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects.(2)The key mechanism of cell growth inhibition by VPA in tumor growth may relate to the induction of cell cycle arrest and apoptosis.(3)VPA can decrease the expression of c-roTe protein and CA-125 protein. VPA may induce differentiation of ovarian cancer SKOV3 cells.(4)VPA can decrease the expression of hTERT.It can inhibit telomerase activity.(5)Treated with VPA combined with DDP can enhance anticancer effects without toxic side effects.(6)This study suggest that VPA could be a perspective and novel attractive agent for treatment of ovarian cancer.