Qiu Yan, Huang Yiqun, Ma Xudong
Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, China.
Zhonghua Xue Ye Xue Za Zhi. 2016 Feb;37(2):144-8. doi: 10.3760/cma.j.issn.0253-2727.2016.02.012.
To investigate the effect of monoamine oxidase inhibitor phenelzine on proliferation, apoptosis and histone modulation in acute lymphoblastic leukemia cell line Molt-4 cells.
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.
① Molt-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. ③ The 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. ④ Phenelzine 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't change the level of histone H3K4me3, H3K9me1, H3K9me2. ⑤ Phenelzine inhibited DNMT1 expression and promoted p15 expression.
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.
探讨单胺氧化酶抑制剂苯乙肼对急性淋巴细胞白血病细胞系Molt-4细胞增殖、凋亡及组蛋白修饰的影响。
采用MTT法检测苯乙肼对细胞增殖的影响；采用流式细胞术检测凋亡率；采用蛋白质免疫印迹法检测凋亡相关蛋白Caspase-3、Bcl-2和Bax、细胞周期蛋白依赖性激酶抑制剂p21、肿瘤抑制蛋白p15的变化，以及组蛋白H3K4、H3K9甲基化和组蛋白H3、DNMT1乙酰化的表达水平。
① 5、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)%，P<0.05。② 10 μmol/L苯乙肼作用24、48、72 h后，细胞增殖率分别为(67.84±3.24)%、(50.24±2.01)%、(40.31±2.25)%，P<0.05。③ 5、10、20 μmol/L苯乙肼作用24 h后，凋亡率分别为(13.64±2.58)%、(31.24±3.42)%、(56.37±4.26)%，呈浓度依赖性。④ 苯乙肼可上调Bax、caspase-3、p21的表达，下调Bcl-2的表达。苯乙肼上调组蛋白H3K4me1、H3K4me2甲基化水平及组蛋白H3乙酰化水平，而对组蛋白H3K4me3、H3K9me1、H3K9me2水平无影响。⑤ 苯乙肼抑制DNMT1表达，促进p15表达。
苯乙肼增加组蛋白H3K4me1、H3K4me2甲基化、组蛋白H3乙酰化及p21表达，降低DNMT1和p15表达，最终抑制Molt-4细胞增殖并诱导凋亡。
