BRD4抑制剂JQ1对Jurkat细胞增殖抑制及凋亡诱导作用的研究

Effect of BRD4 Inhibitor JQl on Proliferation Inhibition and Apotosis Induction in Jurkat Cells

目的:探讨布罗莫结构域抑制剂(JQ1)对急性T淋巴细胞白血病细胞株(Jurkat)的增殖抑制、诱导凋亡作用以及可能的作用机制。方法:应用四甲基偶氮唑蓝(MTT)法检测JQ1作用于Jurkat细胞后的细胞增殖抑制率,Annexin V-FITC/PI荧光染色流式细胞术检测细胞凋亡率的改变,实时荧光定量PCR检测Notch1及c-Myc基因表达水平。结果:随药物浓度的增加,Jurkat细胞生长受到明显抑制,表现为时间-剂量依赖性。JQ1 0.8、1.6、4μmol/L处理Jurkat细胞48和72 h后,Jurkat细胞株的凋亡率呈时间-剂量变化,与对照组比较有统计学差异(P<0.05)。PCR检测显示,药物作用48 h后Notch1及c-Myc mRNA表达均下调,与对照组相比,有显著差异。结论:JQ1可以有效抑制Jurkat细胞株的增殖,这可能是通过Notch1基因和c-Myc基因促进凋亡。JQ1可以作为治疗T-ALL新途径之一。

Objective:To investigate the effect and possible mechanism of bromo-domain inhibitors(JQ1) on proliferation inhibition and inducing apoptosis of acute T lymphocyte leukemia cell line(Jurkat).Methods:Jurkat cell line was treated by JQ1 at different concentrations.MTT was used to detect the cell proliferation inhibition rate.The flow cytometry with AnnexinV-FITC/PI fluorescence staining was used to detect the changes of apoptosis rate,and realtime fluorescent quantitative PCR was used to detect c-Myc/Notchl gene expression levels.Results:With the increasing of drug concentration and prolonging of time,the inhibitory rate of Jurkat cell growth was enhanced in time-dose dependent manner;Jurkat cells was treated by 0.8,1.6,and 4 μ mol/LJQ1 for 48 h and 72 h,the cell apoptosis rate was enhanced with the increase of drug concentration and prolonging of time,and the difference was statistically different in comparison with the control group(P < 0.05);PCR detection indicated that Notchl and c-Myc mRNA expression was reduced in 48 h after JQ1 treatment,which was statistically different from the control group,(P < 0.05).Conclusion:JQ1 can effectively inhibit the growth of Jurkat cell line,and potentially induce apoptosis through Notchl and c-Myc gene.Hence JQ1 may be one of new methods used to treat T-ALL.