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

发布时间：2018-02-11 06:48

本文关键词： 肝细胞癌细胞凋亡内质网应激辛二酰苯胺异羟肟酸　出处：《中国病理生理杂志》2017年12期 　论文类型：期刊论文

【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(P0.05);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(P0.05);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。
[Abstract]:Objective: to investigate the effect of acyl aniline hydroxamic acid on proliferation and apoptosis of human hepatoma cell line HepG2 and its possible mechanism. Methods: HepG2 cells were treated with different concentrations of SAHA for 48 h and analyzed by real-time unlabeled cell analysis. The acetylation levels of histone H3K9 and H3K27 were detected by Western blot. The changes of glucose-regulated protein 78GRP78C, protein kinase R-like endoplasmic reticulum kinase (PERK) and p-PERK protein levels were also observed. Results: compared with the control group, there was no obvious inhibitory effect of 0. 1 and 1 渭 mol/L SAHA on the proliferation of HepG2 cells after 48 h treatment by flow cytometry. The proliferative rate of HepG2 cells in the groups of 6 渭 mol/L SAHA and 12 渭 mol/L SAHA was significantly decreased compared with the control group, and compared with the control group, the proliferation rate of HepG2 cells was significantly decreased. The expression of acH3K9 and acH3K27 increased significantly after 48 h treatment with different concentrations of SAHA, and the expression of pERK was down-regulated, while the protein level of p-PERK was significantly increased by flow cytometry. Conclusion the concentration of SAHA can up-regulate the acetylation modification of histone H3K9 and H3K27 in HepG2 cells, and induce apoptosis of HepG2 cells by activating endoplasmic reticulum stress-related apoptosis pathway.
【作者单位】：贵州医科大学病理生理学教研室;
【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)
【分类号】：R735.7

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