BRD4拮抗剂GSK525762A对SUP-B15细胞增殖与凋亡的影响及其可能的作用机制

Effect of BRD4 Inhibitor GSK525762A on Proliferation and Apoptosis of SUP-B15 Cells In Vitro and Its Possible Mechanism

目的:探讨BRD4拮抗剂GSK525762A对费城染色体阳性急性淋巴细胞白血病SUP-B15细胞株增殖、凋亡的影响及其作用机制。方法:选择不同浓度的GSK525762A处理SUP-B15细胞,采用CCK-8法检测细胞活力并绘制增殖抑制曲线,应用Annexin V/7-AAD双染流式细胞术检测细胞存活与凋亡,定量PCR检测C-MYC、CDK6、BCL2的转录变化。结果:GSK525762A能显著抑制SUP-B15细胞增殖,且具有量-效关系和时-效关系。GSK525762A能够诱导SUP-B15细胞凋亡;GSK525762A能够使抑凋亡基因C-MYC、CDK6、BCL2表达减低。结论:GSK525762A能抑制SUP-B15细胞增殖并诱导其凋亡,其机制主要与下调C-MYC、CDK6、BCL2转录有关。

Objective：To investigate the effect of BRD4 inhibitor GSK525762 A on the proliferation and apoptosis of Philadelphia chromosome-positive acute lymphoblastic leukemia SUP-B15 cells and its mechanism.Methods：SUP-B15 cells were treated with different concentration of GSK525762 A,the proliferation-inhibition curve was assayed and plotted by CCK-8 method,the cell viability and apoptosis were detected by flow cytometry with Annexin V and 7-AAD staining.The transcripts of anti-apoptotic genes C-MYC,CDK6 and BCL-2 were detected by real-time PCR.Results：GSK525762A could inhibit significantly SUP-B15 cell proliteration in dose-and time-dependent manner;GSK525762A treatment could induce apoptosis of SUP-B15 cells.The levels of C-MYC,CDK6 and BCL-2 mRNA transcripts in SUPB15 cells were reduced in GSK525762A-treated group.Conclusion：The GSK525762 A can remarkably inhibit proliferation and induce apoptosis of SUP-B15 cells.The down-regulation of apoptosis-related genes C-MYC,CDK6 and BCL-2may be involved in the process of apoptosis.