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辛伐他汀对急性单核细胞白血病细胞系SHI-1增殖和凋亡的影响

[Effects of simvastatin on proliferation and apoptosis of acute monocytic leukemia cell line SHI-1].

作者信息

Li Yan-Fen, Zhang Ri, Zhang Xu-Hui, Chen Guang-Hua, Cen Jian-Nong, Zhu Zi-Ling

机构信息

Key Laboratory of Thrombosis and Hemostasis Subordinated to Ministry of Health, Jiangsu lnsititute of Hematology, Suzhou University First Affiliated Hospital, Suzhou 215006, Jiangsu Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Jun;19(3):612-6.

Abstract

The purpose of this study was to investigate the effect of simvastatin (SIM) on proliferation and apoptosis of acute monocytic leukemia cell line SHI-1 and its mechanism. Experiments were divided into control and test groups (5 µmol/L, 10 µmol/L, 20 µmol/L SIM groups). The growth inhibitory rate of SHI-1 cells was detected using methyl thiazolyl tetrazolium (MTT) method. The cell cycle distribution and apoptotic rate were measured by using flow cytometry. The expression of BCL-2, caspase-3 mRNA were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression of BCL-2, caspase-3 protein levels were analyzed by Western blot. The results demonstrated that SIM inhibited the growth of SHI-1 cells in time- and does-dependent manners. Cell cycle analysis showed that SHI-1 cells significantly arrested in S phase (p < 0.05) after treating with SIM for 48 hours, as compared with control group. 5 µmol/L SIM in test group significantly blocked cell cycle progression, but can not induce apoptosis. The expressions of BCL-2 mRNA and protein were down-regulated and caspase-3 mRNA and protein were up-regulated along with the increase of SIM concentration (p < 0.05). It is concluded that SIM is able to inhibit proliferation and induce apoptosis of SHI-1 cells, the mechanism may be associated with downregulating the expression of apoptosis-related gene BCL-2, upregulating the expression of caspase-3.

摘要

本研究旨在探讨辛伐他汀(SIM)对急性单核细胞白血病细胞系SHI-1增殖和凋亡的影响及其机制。实验分为对照组和试验组(5 μmol/L、10 μmol/L、20 μmol/L SIM组)。采用甲基噻唑基四氮唑(MTT)法检测SHI-1细胞的生长抑制率。使用流式细胞术测量细胞周期分布和凋亡率。通过逆转录聚合酶链反应(RT-PCR)测定BCL-2、caspase-3 mRNA的表达。通过蛋白质免疫印迹法分析BCL-2、caspase-3蛋白水平的表达。结果表明,SIM以时间和剂量依赖性方式抑制SHI-1细胞的生长。细胞周期分析显示,与对照组相比,用SIM处理48小时后,SHI-1细胞显著停滞于S期(p < 0.05)。试验组中5 μmol/L SIM显著阻断细胞周期进程,但不能诱导凋亡。随着SIM浓度的增加,BCL-2 mRNA和蛋白的表达下调,caspase-3 mRNA和蛋白的表达上调(p < 0.05)。结论是,SIM能够抑制SHI-1细胞的增殖并诱导其凋亡,其机制可能与下调凋亡相关基因BCL-2的表达、上调caspase-3的表达有关。

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