中文摘要：

目的：探讨丙戊酸钠（VPA）协同顺铂（DDP）对人卵巢癌HO8910细胞的杀伤作用及机制。方法：以1μg/m l DDP联合3mmol/L VPA处理细胞,MTT法检测细胞生长抑制率;光镜下观察药物作用下各组细胞形态学的改变;流式细胞术检测细胞周期阻滞情况;RT-PCR法检测p53、p21 mRNA水平表达的改变;W estern blot法检测Ac-H3、p53、p21、Cyclin D1蛋白水平表达的改变。结果：（1）VPA能明显抑制HO8910细胞生长,且呈剂量和时间依赖性,VPA＋DDP处理组抑制率高于DDP处理组,组间差异有统计学意义（P〈0.05）;（2）光镜下观察细胞形态,可见VPA处理组细胞体积缩小呈长梭型,胞膜皱缩,贴壁不良,VPA＋DDP组改变更明显;（3）VPA阻滞卵巢癌HO8910细胞周期于G0/G1期,VPA＋DDP组S期细胞明显减少;（4）VPA及VPA联合DDP均能够明显提高卵巢癌HO8910细胞组蛋白H3的乙酰化水平,上调p53、p21 mRNA及蛋白表达水平,降低CyclinD1蛋白的表达水平,组间差异有统计学意义（P〈0.05）。结论：VPA能够协同DDP杀伤卵巢癌细胞HO8910;其作用机制可能与VPA提高组蛋白乙酰化水平,上调p53、p21基因表达和下调Cyclin D1表达,引发细胞周期阻滞有关。

英文摘要：

Objective：To study the mechanism of which Valproic acid enhance the killing effect of cisplatin on human ovarian cancer cell line HO-8910.Methods：Pretreated with 1μg/ml DDP and 3mmol/L VPA,the growth inhibition ratio of HO-8910 cells was detected with MTT.Morphological changes of cells in each group were observed with inverted microscope.Flow cytometry analyzed the cell cycle changes.The expression of Ac-H3,p53,p21 CyclinD1 gene was deteced by semiquantitative RT-PCR and Western blot.Results：（1）VPA can inhibit HO8910 cell growth in a dose and time-dependent.The suppression ratio of treated with VPA combined DDP was higher than that of DDP treatment（P0.05）.（2）Cell morphology changes can clearly be seen in the VPA group under light microscope：cell volume reduced,change to long spindle,membrane shrinkage,poor adherence.（3）VPA arrest ovarian cancer HO8910 cell cycle at G1 phase,but in VPA＋DDP group G1/G2 phase cells increased as well as S phase decreased.（4）VPA and VPA combination with DDP can significantly enhance the acetylation of Histone H3,increase expression of p53 and p21 and reduce Cyclin D1 expression（P0.05）.Conclusion：VPA can enhance the inhibitory effect of DDP on cell HO8910;The mechanism of action may include increase in the level of histone acetylation and the expression of p53,p21 gene,decrease in the expression of Cyclin D1 and induction of cell cycle arrest.