丙戊酸钠调节组蛋白乙酰化对肝癌细胞浸润转移影响的研究  

Effect of regulating histone acetylized level with VPA on metastasis of hepatocellular carcinoma in vitro

作　　者：赵霞[1] 时昌文[2] 汪运山[3,4] 孙京杰[2] 曹莉莉[2] 李杰[2] 于振海[2] 

机构地区：[1]山东省千佛山医院检验科,山东济南250014 [2]山东省千佛山医院普外中心实验室,山东济南250014 [3]山东省医学科学院,山东济南250061 [4]济南市中心医院中心实验室,山东济南250013

出　　处：《中华肿瘤防治杂志》2009年第2期93-96,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：山东省自然科学基金(2004zx06);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（histone deacetyiase，HDAC）抑制剂丙戊酸钠（valproateacid sodium，VPA）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Transwell小室体外侵袭模型评价HDAC抑制剂VPA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MMP-2、MMP-9蛋白表达来探讨其作用机制。结果：细胞培养24h后，对照组迁移细胞数目较多，为（142±16．5）个，而（0．75～4．0）mmol／L。VPA试验组细胞迁移数目随药物浓度升高而逐渐由（125±12．4）个减少（42±6．1）个，差异有统计学意义，P〈0．001；对照组穿过聚碳酯膜细胞数目（85±7．8）个，明显高于药物实验组（69±6．9～18±3．6）个，差异有统计学意义，P〈0．001；与对照组比较，试验组MMP2、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HDAc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MMP-2和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）. METHODS： The effect of VPA on the metastasis of HepG2 cells was estimated by tumor cell migration and invasion assays. The protein ex pressions of MMP-2 and MMP-9 were detected and analyzed by the indirect immunofluorescence technique. RESULTS： The migration cells on the down-side of transwell membrane in the test groups （142± 16.5） were significantly lower than that those in the control group （decreasing from 125±12.4 to 42± 6.1, as the increasing of VPA from 0.75 mmol/L to 4.0 mmol/L）, P〈0. 001 ;The cells throrgh Transwell in con trol group was 85± 7.8, which was significantly higher than that of test groups （69±6.9-18±3.6）, P〈0.001. The expressions of MMP-2 and MMP9 were down regulated significantly in the experimental groups, meanwhile, they were related with the changes of migration and invasion in the experimental groups. CONCLUSION： Up-regulating histone acetyl izad level by VPA can suppress hepatocellular carcinoma metastasis and invasion, and one of the main mechanisms underlying is down regulating MMP-2 and MMP 9 expressions.

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

分 类 号：R735.7[医药卫生—肿瘤]