VPA Increase The Sensitivity Of Human Ovarian Cancer Cell Line COC1/DDP To Cisplatin In Vitro

Objective:Chemotherapy resistance of malignant tumor is the tough problem to solve now.The drug resistance of ovarian cancer is an important factor in influencing the five year survival rate.Because a few drug such as Verapamil and Tamoxifen bring manifest side effect,their clinical application were limited. There are a lot of researches supporting that the histone deacetylase inhibitors (HDACIs) not only have antitumor effect through many ways,such as inhibiting tumor cell proliferation, including apoptosis,inhibiting tumor angiogenesis and metastasis,cutting down the tumor invasiveness and so on,but also enhance the chemoradion sensitivity of tumor.The mechanisms of chemoradiation sensitivity enhancement of the histone deacetylase inhibitors are complicated and it is not very clear so far. Sodium valproate (VPA) has been used to treat epilepsy for many years.Recently it is found that it can inhibite the histone deacetylase,because it has many good qualities such as long half life,high bioavailability,low valid blood medicine level and few side effects,it shows good perspective.In this study,we investigated the inhibitory effects of VPA combined with cisplatin on the anti-proliferation,apoptotic induction and expression of NF-κB P65 in human ovarian cancer cell line COC1/DDP,and to guide for the clinical medication.Methods:Choosed the human ovarian cancer cell line COC1/DDP as the terget of the study.Cultruled cell in vitro and choosed the cells which were inexponential growth phase.To set up control group,the cisplatin single used group and the connect group. The effects of cisplatin or/and VPA on the proliferation of COC1/DDP were detected by WST-1 assay.The flow cytometry was used to detect the apoptosis rates.The expression of NF-κB was determinded by the immunocytochemical method.Results:The effect of VPA and DDP on cell proliferation (73.25±11.39,82.13±0.72,97.77±1.05)% was more significant compared with those(44.76±2.15,71.64±3.98,93.32±1.98)% treated with DDP only.And the difference have statistical significance (P<0.05).The flowcytometric analysis showed that the apoptotic peak of VPA and DDP(48.50±5.428)% is higher than the group treated with DDP only(23.27±1.93) %. And the difference have statistical significance (P＜0.05).The expression of NF-κB P65 protein increased with DDP used only and decreased obviousely with VPA and DDP. And the difference have statistical significance (P＜0.05).Conclusion:These findings indicated that the histone deacetylase inhibitor VPA inhibited the growth of human ovarian cancer cell line COC1/DDP. Combined treatment with VPA and DDP can increase the sensitivity of COC1/DDP. The expression of NF-κB P65 protein might play an important role in the sensitization enhancement of VPA to chemotherapy-induced apoptosis.