JQ1诱导SUP-B15细胞凋亡的Notch1通路机制研究  

Mechanism of Notchl Pathway in SUP-B15 Cell Apoptosis Induced by JQ1

作　　者：王彦[1] 马梁明[1] 王晓珍[1] 王涛[1] 

机构地区：[1]山西医科大学附属山西大医院血液科,山西太原030001

出　　处：《中国实验血液学杂志》2015年第2期364-368,共5页Journal of Experimental Hematology

摘　　要：目的:本研究观察布罗莫结构域抑制剂JQ1诱导人Ph阳性急性淋巴细胞白血病细胞株(SUP-B15)凋亡的Notch1通路可能机制。方法:用不同浓度JQ1在不同时期处理SUP-B15细胞,用四甲基偶氮唑蓝试验(MTT法)检测细胞增殖情况;用流式细胞术检测细胞周期;实时定量PCR法检测MIS2、Notch1、Hes1、BCR-ABL mRNA的表达水平。结果:JQ1在0-4μmol/L的浓度范围内能抑制SUP-B15细胞的生长,并呈现剂量-时间依赖性;JQ1在1、2、4μmol/L处理SUP-B15细胞48 h后,诱导细胞S期阻滞,并呈剂量依赖性,与同时间对照组比较有统计学差异(P<0.05);与同时间对照组相比,JQ1能够降低MIS2、Notch1、Hes1、BCR-ABL mRNA的表达。结论:JQ1可以有效抑制SUP-B15细胞生长增殖,而Notch1通路凋亡途径很可能是JQ1促进Ph+ALL细胞凋亡的多途径之一。Objective： The study was aimed to investigate the possible mechanism of Notchl pathway in apoptosis of Ph ＋ human ALL Cells（ SUP-B15 cells） induced by bromodomain inhibitors JQ1. Methods： The SUP-B15 cells were treated with different concentrations of JQ1 for different times. The cell proliferation was analyzed with cytotoxicity test （MTT method）. Cell cycle was detected by fluorescence microscopy and flow cytometry. The mRNA expression of MIS2 ,Notchl ,Hesl, BCR-ABL in Notchl pathway was detected by real-time quantitative PCR. Results： JQ1 0 -4 p, mol/L could significantly inhibit the viability of SUP-B15 cells treated in does-and time-dependent manner. After SUP- B15 cells were treated with 1,2,4 μmol/L JQ1 for 48 h, the JQI could induce S cycle arrest in does-dependent manner which was statistical different from the control at the same time （ P 〈 0.05 ）. MIS2, Notchl, Hesl, BCR-ABL mRNA expression was down-regulated by JQ1 which was statistical different from the control（ P 〈 0.05 ）. Conclusion： The JQI can effectively inhibit the growth and proliferation of SUP-B15 cells and the Notchl pathway may be one of the important apoptosis mechanisms in Ph（ ＋ ） ALL cells induced by JQ1.

关 键 词：JQ1 SUP-B15细胞株 Notch1通路 

分 类 号：R733.71[医药卫生—肿瘤]