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[BRD4抑制剂GSK525762A对SUP-B15细胞体外增殖和凋亡的影响及其可能机制]

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

作者信息

Wang Xue, Qi Na, Ma Sha, Yan Zhi-Ling, Wu Qing-Yun, Wang Lin, Chen Chong, Xu Kai-Lin

机构信息

Institute of Hematology, Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.

Department of Hematology, The Affiliated Hospital of Xuzhou Medical College,Xuzhou 221002, Jiangsu Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1654-1658. doi: 10.7534/j.issn.1009-2137.2016.06.008.

Abstract

OBJECTIVE

To investigate the effect of BRD4 inhibitor GSK525762A 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 GSK525762A, 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 SUP-B15 cells were reduced in GSK525762A-treated group.

CONCLUSION

The GSK525762A can remarkably inhibit proliferation and induce apoptosis of SUP-B15 cells. The down-regulation of apoptosis-related genes C-MYC,CDK6 and BCL-2 may be involved in the process of apoptosis.

摘要

目的

探讨BRD4抑制剂GSK525762A对费城染色体阳性急性淋巴细胞白血病SUP - B15细胞增殖和凋亡的影响及其机制。

方法

用不同浓度的GSK525762A处理SUP - B15细胞,采用CCK - 8法检测并绘制增殖抑制曲线,通过Annexin V和7 - AAD染色利用流式细胞术检测细胞活力和凋亡情况。采用实时PCR检测抗凋亡基因C - MYC、CDK6和BCL - 2的转录本。

结果

GSK525762A能以剂量和时间依赖性方式显著抑制SUP - B15细胞增殖;GSK525762A处理可诱导SUP - B15细胞凋亡。GSK525762A处理组SUP - B15细胞中C - MYC、CDK6和BCL - 2 mRNA转录本水平降低。

结论

GSK525762A可显著抑制SUP - B15细胞增殖并诱导其凋亡。凋亡相关基因C - MYC、CDK6和BCL - 2的下调可能参与了凋亡过程。

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