辛伐他汀对急性髓系白血病NB4细胞株DNA甲基转移酶的影响

doi:10.6040/j.issn.1671-7554.0.2014.853

山东大学学报（医学版） ›› 2015, Vol. 53 ›› Issue (6): 28-32.doi: 10.6040/j.issn.1671-7554.0.2014.853

辛伐他汀对急性髓系白血病NB4细胞株DNA甲基转移酶的影响

杨娟¹, 邱宗建², 宋强¹

1. 山东大学齐鲁医院血液科, 山东济南 250012;
2. 福建医科大学附属协和医院血液科, 福建福州 350009

收稿日期:2014-11-21 修回日期:2015-02-28 出版日期:2015-06-10 发布日期:2015-06-10
通讯作者: 宋强。E-mail:qiangs303@sina.com E-mail:qiangs303@sina.com
基金资助:
山东省自然科学基金(Y2006C63)

Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia

YANG Juan¹, QIU Zongjian², SONG Qiang¹

1. Department of Hematology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
2. Department of Hematology, Union Hospital Affiliated to Fujian Medical University, Fuzhou 350009, Fujian, China

Received:2014-11-21 Revised:2015-02-28 Online:2015-06-10 Published:2015-06-10

摘要/Abstract

摘要： 目的探讨辛伐他汀对急性髓系白血病(AML)NB4细胞株DNA甲基转移酶(DNMT)的影响及其作用机制。方法将NB4细胞与不同浓度辛伐他汀(终浓度为0、5、10、15 μmol/L)共处理。DNA甲基转移酶活性/抑制试验测定DNMT活性,采用实时定量PCR法检测DNMT1、DNMT3A、P53 mRNA的表达水平,采用Western blotting法检测DNMT1、DNMT3A、DNMT3B蛋白水平,流式细胞术检测细胞凋亡。结果辛伐他汀处理后,剂量依赖性的DNMT活性下调(P<0.05); DNMT1、DNMT3A mRNA及蛋白水平降低,P53 mRNA表达水平增高(P<0.05),DNMT3B蛋白表达未见明显变化(P>0.05);辛伐他汀促进NB4细胞凋亡。结论辛伐他汀在NB4细胞中可降低DNMT的活性及表达水平并促进细胞凋亡,有望作为DNMT抑制剂治疗急性白血病。

关键词: DNA甲基转移酶, 辛伐他汀, 急性髓系白血病, 去甲基化, NB4细胞株

Abstract: Objective To explore the impacts of Simvastatin (SIM) on DNA methyltransferase (DNMT) of cell line NB4 in acute myeloid leukemia (AML) and to investigate the possible mechanism. Methods NB4 cells were treated with different concentrations of SIM (final concentration 0, 5, 10 and 15 μmol/L). DNMT activities were detected by DNMT activity/inhibition assay. The expressions of DNMT1, DNMT3A and P53 mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of DNMT1, DNMT3A and DNMT3B protein levels were analyzed by Western blotting. The apoptotic rate was measured by flow cytometry. Results The DNMT activity/inhibition assay showed a dose-dependent downregulation of DNMT activities after SIM treatment (P<0.05). The expression levels of DNMT1, DNMT3A mRNA and protein were downregulated while P53 mRNA were upregulated with the increase of SIM concentration (P<0.05). DNMT3B protein level did not change significantly (P>0.05). SIM induced NB4 cell apoptosis. Conclusion Simvastatin can downregulate the DNMT activities and expression levels in AML cell line NB4 and promote cell apopotosis, which may act as a potential DNA-hypomethylating agent for AML.

Key words: Demethylation, NB4 cell line, DNA methyltransferase, Simvastatin, Acute myeloid leukemia

中图分类号:

R551.3

杨娟, 邱宗建, 宋强. 辛伐他汀对急性髓系白血病NB4细胞株DNA甲基转移酶的影响[J]. 山东大学学报（医学版）, 2015, 53(6): 28-32.

YANG Juan, QIU Zongjian, SONG Qiang. Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(6): 28-32.

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辛伐他汀对急性髓系白血病NB4细胞株DNA甲基转移酶的影响

Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia

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