辛二酰苯胺异羟肟酸通过内质网应激凋亡通路诱导HepG2细胞凋亡  

Suberoylanilide hydroxamic acid induces apoptosis of HepG2 cells by endoplasmic reticulum stress apoptotic pathway

作　　者：余蕾[1] 韩冰[1] 田甜[1] 郑璐 杨婷[1] 刘幸[1] 汤雷 罗轩 杨勤[1] 谢汝佳[1] 

机构地区：[1]贵州医科大学病理生理学教研室,贵州贵阳550000

出　　处：《中国病理生理杂志》2017年第12期2151-2156,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81560105);贵州省教育厅自然科学研究项目(黔教合KY字[2014]269);贵州省科技厅基金资助项目(黔科合LH字[2014]7074)

摘　　要：目的:探讨辛二酰苯胺异羟肟酸(SAHA)对人肝癌细胞株HepG2增殖与凋亡的影响及其可能的机制。方法:分别给予不同浓度的SAHA处理HepG2细胞48 h,采用实时无标记细胞分析法检测细胞增殖情况;Western blot法检测组蛋白H3K9和H3K27的乙酰化水平,以及葡萄糖调节蛋白78(GRP78)、蛋白激酶R样内质网激酶(PERK)和p-PERK蛋白水平的变化;流式细胞术检测细胞凋亡。结果:与对照组相比,0.1和1μmol/L SAHA处理48 h对HepG2细胞增殖无明显抑制作用,6和12μmol/L SAHA组HepG2细胞增殖率明显下降(P<0.05);Western blot检测发现,与对照组比较,不同浓度的SAHA处理细胞48 h后,ac H3K9和ac H3K27表达水平明显升高,GRP78蛋白表达显著上调,PERK蛋白表达显著下调,而p-PERK的蛋白水平显著增加(P<0.05);流式细胞术检测发现,随着SAHA浓度的增高,HepG2细胞的凋亡逐渐增加。结论:SAHA可上调HepG2细胞中组蛋白H3K9和H3K27的乙酰化修饰水平,并通过激活内质网应激相关凋亡通路来诱导HepG2细胞发生凋亡。AIM： To investigate the effect of suberoylanilide hydroxamic acid （SAHA） on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells and to explore its possible mechanism. METHODS ： HepG2 cells were treated with SAHA at different concentrations for 48 h. The proliferation of HepG2 cells was detected by real-time cellular analysis. The protein levels of acetylated histones H3K9 and H3K27, glucose-regulated protein 78 （GRP78）, protein kinase R-like endoplasmic reticulum kinase （PERK） and p-PERK were determined by Western blot. The cell apoptosis was analyzed by flow cytometry. RESULTS： Compared with control group, treatment with SAHA at 0. 1 jjimol/L and 1 jjimol/L for 48 h showed no significant inhibitory effect on the proliferation of HepG2 cells, while SAHA at 6 jjimol/L and 12 jjimol/L significantly inhibited the proliferation of HepG2 cells （P 〈0. 0 5 ） . The results of Western blot showed that the protein levels of acH3K9, acH3K27, GRP78 and p-PERK increased significantly after treated with SAHA at diffe-rent concentrations for 48 h, while the protein level of PERK was decreased significantly （P 〈0. 05）. The results of flow cytometry analysis showed that the apoptotic rates of the HepG2 cells increased with the increase in SAHA concentration. CONCLUSION： SAHA up-regulates the acetylation of H3K9 and H3K27 in the HepG2 cells and induces apoptosis of HepG2 cells by activating the endoplasmic reticulum stress-related apoptosis pathway.

关 键 词：肝细胞癌 细胞凋亡 内质网应激 辛二酰苯胺异羟肟酸 

分 类 号：R0[医药卫生] R735.7