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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 phenylhexylisothiocyanate (PHI) on Molt-4 cell line in vitro and to investigate the effect of PHI on the methylation and acetylation of Molt-4 cells. Methods The effects of PHI on the proliferation of Molt-4 cells were observed by MTT assay and clonal inhibition test. Flow cytometry was used to detect the effects of PHI on cell cycle and cell cycle. Western blotting was used to observe the histone acetylation Changes in enzymes, histone methylation and acetylation status. Results PHI upregulated P300 / CBP levels in Molt-4 cells, significantly increased histone H3, H4 acetylation and H3K4 methylation levels, inhibited histone H3K9 expression, and arrested cells in G_0 / G_1 And induce apoptosis. Conclusion PHI may be a histone deacetylase inhibitor, which can regulate histone methylation and affect its epigenetics, which may serve as new anti-leukemia therapeutic agents.