摘要
目的:探讨组蛋白去乙酰化酶抑制剂(HNHA)对人肝癌细胞株HepG2增殖与凋亡的影响及其机制。方法:25μmol/L HNHA处理HepG2细胞24及36 h,采用实时无标记细胞分析仪(RTCA)检测HNHA对HepG2细胞增殖的影响,应用流式细胞仪检测HepG2细胞凋亡情况;采用Western Blot检测HepG2细胞中组蛋白H3K27位点(acH3K27)乙酰化水平、葡萄糖调节蛋白78(GRP78)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、CCAAT/增强子结合蛋白同源蛋白(CHOP)的表达。结果:HNHA处理HepG2细胞后可显著抑制HepG2细胞增殖,并促进HepG2细胞凋亡;Western Blot结果显示25μmol/L HNHA处理HepG2细胞24及36 h时,细胞中acH3K27、GRP78、p-PERK及CHOP蛋白表达水平较对照组显著上调(P<0.05)。结论:HNHA可能通过上调HepG2细胞中组蛋白H3K27位点的乙酰化修饰水平、激活PERK信号通路诱导HepG2细胞凋亡。
Objective： To observe the effect of histone deacetylase inhibitor（ HDACi） on proliferation and apoptosis of human hepatocellular carcinoma cells HepG2 and explore the mechanism of a new HDACi-N-hydroxy-7-（ 2-naphthylthio） heptanomide（ HNHA）. Methods： HepG2 cells were treated with 25 μmol/L for 24 h and 36 h,the proliferation of HepG2 was detected by real time cellular analysis（ RTCA） assay. The apoptosis of HepG2 was determined by flow cytometry. The protein expressions of acH3 K27,GRP78,p-PERK and CHOP were detected by Western blot（ WB）. Results：Compared with the control group,the proliferation of HepG2 cells treated with HDACi decreased significantly,while the apoptosis of HepG2 cells increased more obviously in the study group. After treatment with HNHA for 24 h and 36 h,the expressions of acH3 K27,GRP78,p-PERK and CHOP in HepG2 cells increased more obviously than those in the control group. Conclusion： HNHA could upregulate the acetylation of H3 K27 in HepG2 cells and activate the PERK signaling pathway,which may be involved in the mechanism of apoptosis of HepG2 cells.
作者
罗轩
黄建钊
LUO Xuan;HUANG Jianzhao(Guizhou Medical University,Guiyang 550004,Guizhou,China;People＇s Hospital of Guizhou Medical University,Guiyang 550002,Guizhou,China)
出处
《贵州医科大学学报》
CAS
2018年第5期522-526,共5页
Journal of Guizhou Medical University
基金
贵州省教育厅自然科学研究项目[黔教合KY字(2014)269号]
关键词
组蛋白乙酰化
组蛋白去乙酰化酶抑制剂
肝细胞癌
蛋白激酶R样内质网激酶
细胞凋亡
histone acetylation
histone deacetylase inhibitor
hepatocellular carcinoma
protein kinase-like endoplasmic reticulum protein kinase
apoptosis
