苯乙肼对Molt-4细胞增殖、凋亡及组蛋白甲基化、乙酰化的影响  

Effect of phenelzine on the proliferation, apoptosis and histone methylation and acetylation of Molt-4 cells

作　　者：邱艳[1] 黄轶群[1] 马旭东[1] 

机构地区：[1]福建医科大学附属漳州市医院,漳州363000

出　　处：《中华血液学杂志》2016年第2期144-148,共5页Chinese Journal of Hematology

基　　金：福建省自然科学基金（2012J01420）;福建省医学创新课题（2012-CX.32）;福建省引进重大项目计划基金（201212004）;漳州市科学研究发展计划基金（20100080）;福建医科大学重点科研项目（FZS13004Z）

摘　　要：目的 研究单胺氧化酶抑制剂苯乙肼对急性T淋巴细胞白血病细胞株Molt-4细胞增殖、凋亡及表观遗传学调控的影响.方法 用MTT法检测苯乙肼对Molt-4细胞增殖率的影响,流式细胞术观察苯乙肼对Molt-4细胞凋亡的影响,Western blot法检测caspase-3、Bcl-2、Bax、p21、p15、DNA甲基转移酶1（DNMT1）表达以及组蛋白H3K4、H3K9甲基化及组蛋白H3乙酰化水平.结果 ①5、10、15、20 μmol/L苯乙肼作用24 h后,Molt-4细胞增殖率分别为（87.68±3.54）％、（67.84±3.24）％、（51.48±3.37）％、（28.72±2.56）％,差异有统计学意义（P＜0.05）.②10 μmol/L苯乙肼作用24、48、72 h后,Molt-4细胞增殖率分别为（67.84±3.24）％、（50.24±2.01）％、（40.31±2.25）％,差异有统计学意义（P＜0.05）.③5、10、20 μmol/L苯乙肼作用24 h后,Molt-4细胞的凋亡率分别为（13.64±2.58）％、（31.24±3.42）％、（56.37±4.26）％,差异有统计学意义（P＜0.05）.④苯乙肼上调Bax、caspase-3和p21表达,下调Bcl-2表达,同时上调组蛋白H3K4单甲基化、H3K4二甲基化水平及组蛋白H3乙酰化水平,而对组蛋白H3K4三甲基化、H3K9单甲基化、H3K9二甲基化水平无影响.⑤苯乙肼使Molt-4细胞DNMT1表达下调、p15蛋白表达上调（P＜0.05）.结论 苯乙肼可上调Molt-4细胞组蛋白H3K4单甲基化、H3K4二甲基化和组蛋白H3乙酰化水平并上调p21、p15蛋白表达、下调DNMTl表达,最终抑制Molt-4细胞增殖、诱导细胞凋亡.Objective To investigate the effect of monoamine oxidase inhibitor phenelzine on proliferation,apoptosis and histone modulation in acute lymphoblastic leukemia cell line Molt-4 cells.Methods The effect of Phenelzine on cell proliferation was detected by MTT.Apoptotic rate was measured by flow cytometry.The variation of apoptosis associated proteins Caspase-3,Bcl-2 and Bax,cyclin-dependent kinase inhibitor p21,tumor suppressor protein p15,and the expression level of histone methylation of H3K4,H3K9 and histone acetylation of H3,DNMT1 were detected by Western Blot.Results ①Molt-4 cell proliferation rates were （87.68±3.54）%,（67.84±3.24）%,（51.48±3.37）%,（28.72±2.56）% respectively after exposured to phenelzine at 5,10,15,20 μmol/L for 24 h,P〈0.05.（② After 10 μmol/L of phenelzine exposure for 24,48,72 h,cell proliferation rates were （67.84±3.24）%,（50.24±2.01）%,（40.31±2.25）%,P〈0.05.③The apoptotic rates were （13.64±2.58）%,（31.24±3.42）%,（56.37 ± 4.26）% after phenelzine treatment at 5,10,20 μmol/L for 24 h,which was concentration dependent.④Phenelzine could upregulate the expression of Bax,caspase-3,p21,and downregulate Bcl-2 expression.Phenelzine upregulated the methylation level of histone H3K4me1,H3K4me2 and histone acetylated H3,while it didn＆#39;t change the level of histone H3K4me3,H3K9me1,H3K9me2.⑤Phenelzine inhibited DNMT1 expression and promoted p15 expression.Conclusions Phenelzine increased the methylation of histone H3K4me1,H3K4me2,acetylation of histone H3 and p21,and decreased the expression of DNMT1 and p15,and ultimately inhibited the proliferation and apoptosis of Molt-4 cells.

关 键 词：苯乙肼 甲基化 组蛋白类 乙酰化作用 MOLT-4细胞 

分 类 号：R733.7[医药卫生—肿瘤]