摘要
目的研究异硫氰酸苯己酯(PHI)在体外对淋巴细胞白血病 Molt-4细胞系的作用,观察 PHI 对 Molt-4细胞组蛋白甲基化、乙酰化调控的影响。方法采用 MTF 法、克隆抑制实验观察 PHI对 Molt-4细胞增殖的影响;采用流式细胞术检测 PHI 诱导细胞凋亡和对细胞周期的影响;用 Westernblot 法观察 PHI 作用后细胞的组蛋白乙酰化酶、组蛋白甲基化及乙酰化状态的变化。结果 PHI 可上调 Molt-4细胞组蛋白乙酰化酶 P300/CBP 水平,显著提高组蛋白 H3、H4乙酰化及 H3K4甲基化水平,抑制组蛋白甲基化 H3K9表达,阻滞细胞于 G_0/G_1期,并诱导细胞凋亡。结论 PHI 可能是一种组蛋白去乙酰化酶抑制剂,同时能调控组蛋白甲基化,影响其表观遗传学,可能作为新的抗白血病治疗药物。
Objective To investigate the effect of phenylhexyl isothiocyanate （PHI）on acetylation and methylation of histone in acute lymphoblastic leukemia cell line Molt4. Methods The inhibition of cell proliferation was observed by MTT method and clone suppression test. Apoptosis and cell cycle arrest were measured by flow cytometry. The alterations in histone acetyhransferase and acetylations and methylations of histones were detected by Western blot. Results PHI could up-regulate the expression of acetyhransferase （P300/CBP）, markedly induced the accumulation of acetylated histone H3, H4 and methylated histone H3 lysine 4（H3K4） , and inhibited methylation on lysine 9 of H3 （H3K9）. The epigenetic regulation resulted in cell cycle arrest at G0/G1 phase, and induction of apoptosis. Conclusions PHI can modulate both histone methylation and acetylation. It may serve as a histone deacetylase inhibitor, and might be a potential novel anti-leukemia agent.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2007年第9期612-615,共4页
Chinese Journal of Hematology
作者简介
通信作者：马旭东，Email：maxudong005@hotmail．com
