CAJ | 학술논문

目的观察布罗莫结构域4(brd4)抑制剂JQ1对Ph阳性急性淋巴细胞白血病(Ph+ALL)细胞株SUP-B15的增殖抑制、凋亡作用及对brd4及其下游基因myc、p53表达的影响,探讨其是否对bcr-abl有逆转作用.方法采用不同浓度的JQ1处理SUP-B15细胞.四甲基偶氮唑蓝(MTT)法检测细胞的增殖抑制率;AnnexinV-FITC/PI荧光染色流式细胞术检测细胞凋亡率;实时荧光定量PCR(RT-PCR)法检测bcr-abl、brd4 、myc 、p53的mRNA表达.结果不同浓度的JQ1均能抑制SUP-B15细胞的增殖,诱导细胞发生凋亡,凋亡率较对照组明显增高,并呈时间-剂量依赖性,作用72 h半数抑制浓度为1.0 μmol/L.同时JQ1可以使bcr-abl、 brd4、 myc的mRNA水平下降,而使p53 mRNA的水平升高.结论 brd4抑制剂JQ1可通过下调brd4的表达,影响其下游基因myc及p53的表达,同时逆转bcr-abl表达,达到抑制Ph+ ALL细胞增殖、诱导细胞凋亡的作用.
목적 관찰포라막결구역4(brd4)억제제JQ1대Ph양성급성림파세포백혈병(Ph+ALL)세포주SUP-B15적증식억제、조망작용급대brd4급기하유기인myc、p53표체적영향,탐토기시부대bcr-abl유역전작용.방법 채용불동농도적JQ1처리SUP-B15세포.사갑기우담서람(MTT)법검측세포적증식억제솔;AnnexinV-FITC/PI형광염색류식세포술검측세포조망솔;실시형광정량PCR(RT-PCR)법검측bcr-abl、brd4 、myc 、p53적mRNA표체.결과 불동농도적JQ1균능억제SUP-B15세포적증식,유도세포발생조망,조망솔교대조조명현증고,병정시간-제량의뢰성,작용72 h반수억제농도위1.0 μmol/L.동시JQ1가이사bcr-abl、 brd4、 myc적mRNA수평하강,이사p53 mRNA적수평승고.결론 brd4억제제JQ1가통과하조brd4적표체,영향기하유기인myc급p53적표체,동시역전bcr-abl표체,체도억제Ph+ ALL세포증식、유도세포조망적작용.
Objective To observe the effect of bromodomain4 (brd4) inhibitor JQ1 on proliferation inhibition and apoptosis of Ph positive acute lymphocytic leukemia (Ph+ ALL) cells, and to explore the influence on the expression of brd4 and its downstream genes (myc and p53), and the reverse effect on bcr-abl.Methods Different concentrations of JQ1 were used on SUP-B15 cells.The proliferation inhibition rate was detected by MTT, the apoptosis rate was determined by flow cytometry (FCM), and the expressions of bcr-abl mRNA, brd4 mRNA, myc mRNA and p53 mRNA were detected by real-time fluorescent quantitative PCR (RT-PCR).Results Different concentrations of JQ1 inhibited SUP-B15 cells proliferation and induced cell apoptosis.The apoptosis rate was significantly increased compared with that in control group with a time-dose dependent manner.Median inhibitory concentration at 72 h was 1.0 pmol/L.At the same time, JQ1 decreased the transcription levels of bcr-abl mRNA, brd4 mRNA and myc mRNA, and increased the transcription level of p53 mRNA.Conclusions As a brd4 inhibitor, JQ1 can decrease the expression of brd4 to affect the expression of its downstream genes myc and p53, meanwhile, it can change the over expression of bcr-abl to suppress the proliferation of Ph+ ALL cells and induce apoptosis.