组蛋白乙酰化水平对肝癌细胞迁移和侵袭能力的影响

摘要

Objective:To observe the acetylation levels of histone H3K9,H4K12 and H4K16 in hepatocellular carcinoma cells (HCC),and its effects on the motility and invasion of HCC.Methods:LO2,a normal liver cell line,and HEPG2,MHCC97L,HCCLM3 with different metastasis potential,were detected by Western blot experiment to determine the histonhe acetylation levels of H3K9,H4K12 and H4K16,the alteration of the acetylation after HCC were treated by suberoylanilide hydroxamic acid (SAHA),a acetylation inhibitor,for 24 h and 48 h.The migration and invasion ability of the cells were exploited by Transwell migration and Matrigell invasion assay after the cells were interfered with SAHA.Result:The acetylated levels of H3K9,H4K12 and H4K16 were reduced to HepG2,MHCC97L and HCCLM3,compared with LO2;SAHA raised the acetylation levels of H3K9,H4K12 and H4K16 in HCCLM3 and inhibited the mobility of HCC.Conclusion:The de-acetylation of H3K9,H4K12 and H4K16 may involve in hepatoma's occurrence and metastasis,and the migration and invasion of HCC can be inhibited by deacytlation inhibitor.%目的:观察人肝细胞株LO2及不同转移能力的肝癌细胞株HepG2、MHCC-97L和LM3中组蛋白H3K9、H4K12及H4K16位点的乙酰化水平,并探讨组蛋白乙酰化对肝癌细胞迁移、侵袭能力的影响.方法:采用Western blot实验检测LO2、HepG2、MHCC-97L和LM3中组蛋白H3K9、H4K12及H4K16乙酰化水平;应用组蛋白去乙酰化酶抑制剂伏立诺他(SAHA,1.5 μmol/L和3μmol/L)处理肝癌LM3细胞株24 h、48 h后,Western blot检测其组蛋白H3K9、H4K12及H4K16乙酰化水平变化,transwell实验检测细胞迁移、侵袭能力的变化.结果:H3K9、H4K12及H4K16乙酰化水平由高到低为HepG2、MHCC-97L、LM3,3种肝癌细胞株的乙酰化水平均低于人肝细胞LO2(P ＜0.05);去乙酰化酶抑制剂SAHA作用后,LM3细胞组蛋白H3K9、H4K12及H4K16乙酰化水平明显提高,细胞的迁移、侵袭能力明显降低,与未用SAHA处理的LM3细胞比较,差异有统计学意义(P＜0.05).结论:提高组蛋白H3K9、H4K12、H4K16位点的乙酰化水平,能抑制肝癌细胞的迁移、侵袭能力.