|本期目录/Table of Contents|

[1]周蕾,王茜,李丹丹,等.Tenovin-6 对AML1/ETO (+) 急性髓系白血病细胞的增殖抑制和促凋亡作用[J].慢性病学杂志,2015,(02):150-154.
 ZHOU Lei*,WANG Qian,LI Dan-dan,et al.Effects of a histone deacetylase inhibitor, tenovin-6, against cellular proliferation and promoting apoptosis in AML1-ETO-positive acute myeloid leukemia cells[J].,2015,(02):150-154.
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Tenovin-6 对AML1/ETO (+) 急性髓系白血病细胞的增殖抑制和促凋亡作用(PDF)

《慢性病学杂志》[ISSN:1674-8166/CN:11-5900/R]

卷:
期数:
2015年02期
页码:
150-154
栏目:
论著
出版日期:
2015-04-30

文章信息/Info

Title:
Effects of a histone deacetylase inhibitor, tenovin-6, against cellular proliferation and promoting apoptosis in AML1-ETO-positive acute myeloid leukemia cells
作者:
周蕾12 王茜1 李丹丹1 张晓东2 王立军1 王莉莉1 于力1 窦立萍1
1. 解放军总医院血液科,北京100853;2. 解放军第二○ 二医院血液科,沈阳110083
Author(s):
ZHOU Lei* WANG Qian LI Dan-dan ZHANG Xiao-dong WANG Li-jun WANG Li-li YU Li DOU Li-ping
*Department of hematology, Chinese PLA General Hospital, Beijing 100853, China Corresponding author: DOU Li-Ping, E-mail: lipingruirui@163.com
关键词:
组蛋白去乙酰化酶抑制剂Tenovin-6AML1/ETO急性髓系白血病细胞增殖细胞凋亡
Keywords:
Histone deacetylase inhibitor Tenovin-6 AML1-ETO fusion protein Acute myeloid leukemia Cellular proliferation Apoptosis
分类号:
R587.24
DOI:
-
摘要:
目的观察组蛋白去乙酰化酶抑制剂(HDACi)Tenovin- 6 对人AML1/ETO (+) 急性髓系白血病 (AML)细胞的增殖、细胞凋亡及周期的影响。方法用CCK- 8 法及克隆形成试验检测Tenovin- 6 对 AML1/ETO (+) AML 细胞增殖活性的影响;流式细胞仪检测不同浓度Tenovin-6 作用于细胞后细胞凋 亡、细胞周期的变化;并与AML1/ETO (-) AML 细胞系进行比较。结果Tenovin-6 对AML1/ETO (+) AML 细胞有增殖抑制作用, 其抑制作用呈现为时间和浓度依赖性, 并使细胞克隆形成能力下降; Tenovin-6 可以促进AML1/ETO (+) AML 细胞凋亡,并诱导细胞周期阻滞于G1 期,表现为G1 期细胞比 例升高,而G2/M 及S 期细胞比例下降,且与AML1/ETO (-) AML 细胞系相比较具有更高的敏感性。 结论Tenovin-6 能抑制AML1/ETO (+) AML 细胞增殖, 诱导细胞凋亡, 使周期阻滞于G1 期, 并较 AML1/ETO (-) AML 细胞系具有更高的敏感性。
Abstract:
Objective To investigate the effects of Tenovin- 6, a sort of Histone Deacetylase Inhibitor (HDACi), on the proliferation, apoptosis and cell cycles of AML1-ETO-Positive Acute Myeloid Leukemia (AML) cells. Methods Cell proliferation was measured by Cell Counting Kit- 8 (CCK- 8) and Clonality Assays. Both cell apoptosis and cell cycles were analyzed using Flow Cytometry method. Results were compared to AML1-ETO-Negtive AML cells. Results Tenovin-6 inhibited cellular proliferation in a time-dependent and dose-dependent manner in vitro and reduced colony formation. Tenovin- 6 induced apoptosis in AML1-ETO-Positive AML cell lines and evoked partial cell cycles arresting in G1 phase, which included the accumulation of cell rates in G1 phase and reduction of cell rates in G2/M phase and S phase. AML1- ETO- Positive AML cells were more sensitive to Tenovin- 6 doses than AML1- ETO- Negtive AML cells. Conclusions Tenovin- 6 could inhibit cellular proliferation, evoke partial cell cycle arresting in G1 phase, and induce apoptosis in AML1-ETO-Positive AML cell lines and have more effects compared to AML1-ETO-Negtive AML cells.

参考文献/References:

[1] Grisolano JL, O'Neal J, Cain J, et al. An activated receptor ty? rosine kinase, TEL/PDGFbetaR, cooperates with AML1- ETO to induce acute myeloid leukemia in mice [J]. Proc Natl Acad Sci U S A, 2003,100(16):9506-9511.
[2] Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cuta? neous T- cell lymphoma (CTCL) [J]. Blood, 2007,109(1): 31-39.
[3] Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T- cell lymphoma [J].J Clin Oncol, 2007,25(21):3109-3115.
[4] Jang KY, Hwang SH, Kwon KS, et al. SIRT1 expression is associated with poor prognosis of diffuse large B- cell lympho? ma [J].Am J Surg Pathol, 2008,32(10):1523-1531.
[5] Yuan H, Wang Z, Li L, et al. Activation of stress response gene SIRT1 by BCR- ABL promotes leukemogenesis [J]. Blood, 2012,119(8):1904-1914.
[6] Sasca D, Hahnel PS, Szybinski J, et al. SIRT1 prevents geno? toxic stress- induced p53 activation in acute myeloid leukemia [J].Blood, 2014,124(1):121-133.
[7] Wang Z, Yuan H, Roth M, et al. SIRT1 deacetylase promotes acquisition of genetic mutations for drug resistance in CML cells [J]. Oncogene, 2013,32(5):589-598.
[8] 王茜, 窦立萍, 李永辉,等.SIRT1 启动子表达调控载体的构建 和活性分析及AML1-ETO 对其转录活性的影响[J].中国 实验血液学杂志,2015. 23(1):12-18.
[9] Lin RJ, Nagy L, Inoue S, et al. Role of the histone deacetylase complex in acute promyelocytic leukaemia [J]. Nature, 1998,391:811–814.
[10] Gelmetti V, Zhang J, Fanelli M, et al. Aberrant recruitment of the nuclear receptor corepressor– histone deacetylase complex by the acute myeloid leukemia fusion partner ETO [J]. Mol Cell Biol, 1998,18(12):7185–7191.
[11] Martens JH, Brinkman AB, Simmer F, et al. PML- RARal? pha/RXR alters the epigenetic landscape in acute promyelocyt? ic leukemia [J].Cancer Cell, 2010,17(2):173–185.
[12] Li L, Wang L, Li L, et al. Activation of p53 by SIRT1 inhibi? tion enhances elimination of CML leukemia stem cells in com ? bination with imatinib [J].Cancer cell, 2012,21(2):266-281.

备注/Memo

备注/Memo:
基金项目: 国家自然科学基金资助项目( 30800482, 81270610, 81170518, 30971297 ); 北京市科技新星计划项目 (2011114 );北京市自然科学基金资助项目(7132217);军队高新技术项目(2010gxjs091) 作者简介: 周蕾,硕士,主治医师,从事白血病诊治研究 通信作者: 窦立萍,E-mail: lipingruirui@163.com
更新日期/Last Update: 2015-04-15