组蛋白脱乙酰酶抑制剂丙戊酸钠对胃癌细胞浸润转移的影响

The effect of histone deacetylase inhibitor VPA to invasion and metastasis of gastric carcinoma cells

目的 探讨组蛋白脱乙酰酶抑制剂丙戊酸钠对胃癌细胞侵袭、迁移能力的影响及其作用机制.方法 采用肿瘤细胞体外迁移实验和Tanswell小室侵袭模型评价丙戊酸钠对BGC-823细胞浸润转移能力的影响.同时检测BGC-823细胞中MMP-2、MMP-9的表达来探讨其作用机制.结果 对照组细胞培养24小时后迁移细胞数目较多,而丙戊酸钠试验组细胞迁移数目随药物浓度升高而逐渐减少（p〈0.001）;对照组穿过聚碳酯膜细胞数目明显高于药物实验组,差异具有显著意义（p〈0.001）;与对照组比较,试验组MMP-2、MMP-9蛋白表达被明显下调.结论 组蛋白脱乙酰酶抑制剂丙戊酸钠可显著抑制胃癌细胞侵袭转移,通过调节染色体组蛋白乙酰化水平下调金属基质蛋白酶（MMP-2、MMP-9）表达可能是其发挥作用的主要机制之一.

Objective To investigate the suppress effect on gastric carcinoma metastasis and invasion by a selective inhibitor of HDACs - Valproate acid sodium（VPA）. Furthermore, MMP- 2 and MMP- 9 expression was examined to explore the mechanism underlying. Methods The effect of VPA on the metastasis of BGC - 823 cells was evaluated by tumor cell migration and invasion assays. The protein expression of MMP - 2 and MMP - 9 was analyzed by indirect technique. Results The migration cells and cells on the down - side of transwell membrane in the test groups were significantly lower than in the control group（p 〈 0.001） ;Expression of MMP - 2 and MMP - 9 was down regulating significantly in experimental groups. Conclusions VPA can suppress metastasis and invasion of BGC - 823 cells, and one of the main mechanism underlying was down regulating MMP - 2, MMP - 9 expressions.