Sirt1去乙酰化酶抑制剂诱导成人白血病细胞系MT2生长阻滞及凋亡

目的:研究Sirtuin1(Sirt1)去乙酰化酶抑制剂对成人T细胞白血病细胞系MT2增殖及存活的影响。方法:采用RT-PCR方法,比较了成人白血病细胞系MT2与其他两种白血病细胞系(Jurkat,MOLT-4)中Sirt1 mRNA表达水平;通过Sirt1抑制剂尼克酰胺(Nicotinamide)处理MT2细胞后,观察其细胞形态学的变化,并采用MTT、流式细胞术等方法检测Nico-tinamide对MT2细胞增殖、细胞周期及凋亡的影响。结果:成人白血病细胞系MT2中Sirt1表达水平明显高于Jurkat细胞系(P<0.05),而与MOLT-4细胞系无明显差异;抑制Sirt1的去乙酰化酶活性能明显抑制MT2细胞的增殖,引起细胞G2/M期阻滞,诱导细胞凋亡;镜下观察到细胞膜皱缩、卷曲及破裂等凋亡样形态改变。结论:抑制Sirt1去乙酰化酶活性可能是治疗成人T细胞白血病的可行途径之一。

The growth arrest and apoptosis of adult T-cell leukemia cell lines MT2 induced by Sirt1 deacetylases inhibitor

Objective:To study the effect of Sirt1 deacetylase inhibitor on the survival and proliferation of adult T-cell leukemia(ATL) cell line MT2.Methods:The expression of Sirt1 mRNA was detected by RT-PCR in several T-cell leukemia cell lines.After cells were treated with Sirt1 inhibitor Nicotinamide,the morphologically changes of MT2 cells was observed,and cell proliferation,cell cycle arrest and cell apoptosis were measured by MTT and flow cytometry assays.Results: Compared to Jurkat cells,the level of Sirt1 mRNA was significantly higher in adult T-cell leukemia cell line MT2(P<0.05),whereas compared to MOLT-4 cells,there was not significant difference.The Sirt1 inhibitor could obviously inhibit MT2 cell viability,cause cell arrest in G2/M phase and induce cell apoptosis.The apoptotic-like changes of cell morphology including the shrinkage,coiling and disruption of cell membrane were observed by inverted phase contrast microscope.Conclusion:The inhibition of Sirt1 deacetylase may be one of feasible strategies for the therapy of ATL.