[组蛋白去乙酰化酶抑制剂司立亚丁对IM9细胞系的作用及其机制]

[Effects of HDAC Inhibitor Scriptaid on IM9 Cell Line and Its Mechanism].

作者信息

Liu Lin-Lin, Sun Xiao-Yang, Xie Yu, Han Dan-Yang, Yao Ruo-Si, Xu Kai-Lin

机构信息

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

Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Aug;26(4):1116-1121. doi: 10.7534/j.issn.1009-2137.2018.04.029.

DOI:10.7534/j.issn.1009-2137.2018.04.029

PMID:30111417

Abstract

OBJECTIVE

To study the effect of HDAC inhibitor Scriptaid on multiple myeloma IM9 cells and preliminarily clarify the mechanism of Scriptaid-induced cell apoptosis.

METHODS

The cell viability, cell cycle and cell apoptosis were measured by CCK8 assay and flow cytometry respectively, the relative target gene expression levels were detected by RT-PCR, the effect of Scriptaid on p21 promoter activity was detected by using luciferase reporter assay.

RESULTS

Scriptaid inhibited IM9 cell viability in a dose-dependent manner. Scriptaid induced IM9 cell cycle arrest at G/M phase in a dose-dependent manner. Scriptaid triggered IM9 cell apoptosis was obviously, the mRNA levels of apoptosis-related proteins Caspase 9, Caspase 3 and PARP1 were also activated. The apoptosis-associated factors BAD, PTEN and p21 increased following treatment with different dose of Scriptaid, meanwhile, p21 promoter activity was also activated significantly.

CONCLUSION

HDAC inhibitor Scriptaid can promote IM9 cell apoptosis by transcriptional activation of p21 promoter in concentration-dependent manner.

摘要

目的

研究组蛋白去乙酰化酶（HDAC）抑制剂司立他汀对多发性骨髓瘤IM9细胞的作用，并初步阐明司立他汀诱导细胞凋亡的机制。

方法

分别采用CCK8法和流式细胞术检测细胞活力、细胞周期和细胞凋亡情况，采用逆转录-聚合酶链反应（RT-PCR）检测相关靶基因表达水平，利用荧光素酶报告基因检测法检测司立他汀对p21启动子活性的影响。

结果

司立他汀以剂量依赖方式抑制IM9细胞活力。司立他汀以剂量依赖方式诱导IM9细胞周期阻滞于G/M期。司立他汀明显触发IM9细胞凋亡，凋亡相关蛋白半胱天冬酶9（Caspase 9）、半胱天冬酶3（Caspase 3）和聚（ADP-核糖）聚合酶1（PARP1）的mRNA水平也被激活。不同剂量司立他汀处理后，凋亡相关因子BAD、PTEN和p21增加，同时p21启动子活性也显著激活。