单胺氧化酶抑制剂苯乙肼对套细胞淋巴瘤细胞生长增殖的影响及相关机制研究  

Effect of Monoamine Oxidase Inhibitor Phenelzine on Proliferation of Mantle Cell Lymphoma and Its Mechanism

作　　者：詹丽芬[1] 黄轶群[2] 陈强[3] 马旭东[2] 

机构地区：[1]福建医科大学附属漳州市医院肿瘤科,福建漳州363000 [2]福建医科大学附属漳州市医院血液科,福建漳州363000 [3]福建医科大学附属协和医院肿瘤科,福建福州350001

出　　处：《中国实验血液学杂志》2017年第4期1030-1035,共6页Journal of Experimental Hematology

基　　金：福建省引进重大项目计划基金(2012I2004);福建省自然科学基金(2012J01420);福建医科大学科学研究专项基金项目(重点类)(2013FZS13004Z);福建省医学创新课题(2012-CX-32)

摘　　要：目的:研究单胺氧化酶抑制剂苯乙肼在体外对套细胞淋巴瘤Jeko-1细胞的增殖抑制作用及其可能的作用机制。方法:应用MTT方法绘制细胞生长曲线,应用流式细胞术观察细胞凋亡;Western blot检测凋亡相关蛋白Caspase-3、Bcl-2、Bax及P21蛋白表达水平的变化,组蛋白H3K4单甲基化、双甲基化、三甲基化及组蛋白H3乙酰化状态的变化,以及Wnt信号转导通路相关蛋白表达水平的变化。结果:单胺氧化酶抑制剂苯乙肼可上调Bax、caspase-3、P21蛋白表达,下调Bcl-2,抑制Jeko-1细胞增殖,诱导细胞凋亡,并呈浓度依赖性(r=0.981);苯乙肼上调Jeko-1细胞组蛋白H3K4me1和H3K4me2水平及H3乙酰化水平,而组蛋白H3K4me3水平无明显改变;苯乙肼处理24 h后Jeko-1细胞的WNT通路蛋白p-GSK-3β、β-catenin、c-myc、cyclin D1表达均下降(P<0.05)。结论:单胺氧化酶抑制苯乙肼能调控组蛋白甲基化、乙酰化,抑制Wnt/β-catenin信号转导通路,从而诱导细胞凋亡、抑制细胞增殖,有望成为套细胞淋巴瘤的靶向治疗药物。Objective：Abstract To investigate the effect of monoamine oxidase inhibitor phenelzine on in vitro growth was and Methods：of cell of mantle cell lymphoma Jeko-1 cells and its possible The mechanism.apoptosis proliferation observe MTT assay flow used to the proliferation and to draw a and growth Wnt curve.signal cell was the measured level by cytometry.of The were expressions apoptosis-related protein pathway as well and as of acetylation histone Results：by Western way blot.analyzed Phenelzine inhibited apoptosis proliferation promoted apoptosis of Jeko-1 cells in a dosedependent protein BAX,Caspase-3 and p21,while decreasing antiapoptotic by increasing the expression of related BCL-2.In addition,phenelzine could H3K4mel,H3K4me2 protein upregulate histone and histone acetylated H3,without affecting hitone H3K4me3.Moreover,phosphorylation GSF-3β,β-catenin,c-myc and cyclinD1 of Conclusion：decreased induce exposure to phenelzine for 24 hours.after Phenelzine can inhibit Jeko-1 cell proliferation and/β-catenin signal pathway,apoptosis by regulating methylation and acetylation lymophma.of histone and suppressing Wnt suggesting its therapeutic benefit for mantle cell

关 键 词：单胺氧化酶抑制剂 苯乙肼 套细胞淋巴瘤 组蛋白甲基化 WNT信号转导通路 

分 类 号：R733.1[医药卫生—肿瘤]