调节组蛋白乙酰化修饰对肝癌细胞浸润转移的影响  

Effect of Regulating histone acetylizad level with VPA on Metastasis of Hepatocellular Carcinoma In Vitro

作　　者：时昌文[1] 汪运山[1] 曹莉莉[2] 孙京杰[2] 

机构地区：[1]山东省医学科学院,济南250014 [2]山东省千佛山医院,济南250014

出　　处：《医学检验与临床》2008年第1期19-21,共3页Medical Laboratory Science and Clinics

基　　金：山东省卫生科技发展计划青年基金项目(2007QZ019)

摘　　要：目的 探讨应用组蛋白脱乙酰酶抑制剂VIA调节组蛋白乙酰化水平对肝细胞性肝癌细胞侵袭、迁移能力的影响及其可能作用机制.方法 采用肿瘤细胞体外迁移实验和Tanswell小室体外侵袭模型评价组蛋白脱乙酰酶抑制剂丙戊酸钠对HepG2细胞浸润转移能力的影响.进一步应用间接免疫荧光技术检测HepG2细胞中MMP-2、MMP-9的表达来探讨其作用机制.结果 细胞培养24小时后,对照组迁移细胞数目较多,而0.75-4.0mmol/L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,并且与肿瘤细胞迁移、侵袭的变化密切相关.结论 应用组蛋白脱乙酰酶抑制剂逆转染色体组蛋白低乙酰化水平可显著抑制肝癌细胞侵袭转移,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 hepatocellular carcinoma metastasis and invasion by up-regulating histone acetylizad level with a selective inhibitor of HDACs-Valproate acid sodium(VPA).Furthermore,MMP-2 and MMP-9 expression was examined todetected the mechanism underlying.Methods The effect of VPA on the metastasis of HepG2 cells was evaluated by tumor cell migration and invasion assays.The protein expression of MMP-2 and MMP9 was analyzed by indirect immunofluorescence 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,meanwhile,it is related with the changes of migration and invasion in experimental groups.Conclusions Up-regulating histone acetylizad level by VPA can suppress hepatocellular carcinoma metastasis and invasion,and one of the main mechanism underlying was down regulating MMP-2,MMP-9 expression.

关 键 词：肝肿瘤 侵袭 组蛋白脱乙酰酶抑制剂 肝癌细胞系 丙戊酸 金属基质蛋白酶 

分 类 号：R735.7[医药卫生—肿瘤]