首页|辛伐他汀对急性早幼粒细胞白血病NB4细胞NF-κB信号通路的影响

辛伐他汀对急性早幼粒细胞白血病NB4细胞NF-κB信号通路的影响

Effects of simvastatin on NF-κB signaling pathways in human acute promyelocytic leukemia NB4 cell line

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目的 探讨辛伐他汀对人急性早幼粒细胞白血病细胞株(NB4细胞)增殖与凋亡的影响以及对凋亡信号转导通路NF-κB通路相关基因mRNA表达的影响,以探讨辛伐他汀抗白血病效应及可能机制.方法 以不同浓度辛伐他汀处理NB4细胞,取对数生长期细胞进行实验.实验分为阴性对照组和辛伐他汀处理组(终浓度分别为5、10、15 μmol/L),培养24、48、72 h.采用MTT法观察NB4细胞增殖能力;流式细胞术测定NB4细胞凋亡指标AnnexinⅤ/propidium iodide变化;PCR芯片研究NB4细胞NF-κB通路相关基因mRNA的差异表达.结果 辛伐他汀对NB4细胞的生长有明显抑制作用和促凋亡作用(均P<0.01),且呈时间与剂量依赖性.15 μmol/L辛伐他汀处理NB4细胞24、48、72 h细胞抑制率分别达到45.75%、92.91%、96.46%,而细胞早期凋亡率分别为30.25%、64.34%、87.38%.与对照组相比,15 μmol/L辛伐他汀处理NB4细胞48 h组中NF-κB通路有56个基因表达发生改变,其中47个基因表达下调、9个基因表达上调.结论 辛伐他汀能抑制NB4细胞增殖并诱导其凋亡,其诱导凋亡机制可能与辛伐他汀调节NF-κB通路相关基因的表达有关.
Objective To investigate the effects of simvatatin on proliferation, apoptosis, the NF-κB signaling pathway in human acute promyelocytic leukemia cell lines NB4. Methods NB4 cells were incubated with different concentration of simvastatin (5 ,10,15 μmol/L) , NB4 cells without any treatment were as control. Cells of different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to evaluate the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis and necrosis ratio. The human NF-κB signaling pathway RT2 profiler PCR array profiles the expression of genes involved in NF-κB signaling. Results Simvastatin inhibited the proliferation and induced the apoptosis of NB4 cells in time and dose-dependent manner significantly ( all P < 0. 01). The cell growth inhibition rate of NB4 cells treated with 15μmol/L simvastatin were 45. 75% , 92. 91% and 96.46% respectively at 24, 48 and 72 h; and the early stage apoptosis ratio were 30.25% , 64. 34% and 87. 38% , respectively. Compared with the control group, 56 genes expression levels changed in the group of 15 μmol/L simvatatin group at 48 h, among which, 47 genes were down-regulated and 9 genes were up-regulated. Conclusion Simvatatin potentially inhibited proliferation and induce apoptosis of NB4 cells, and the mechanism may be associated with the changes of gene expression levels involved in NF-κB signaling pathway regulated by simvastatin.

simvastatinNB4 cellcell proliferationapoptosisNF-κB signaling pathwayPCR array

华晓莹、曾梅、江庭秀、顾伟英、邱国强、李曼、王志林、曹祥山

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苏州大学附属第三医院血液科,江苏常州213000

昆山市第一人民医院血液科,江苏昆山215300

广西医科大学附属第四医院血液科,广西柳州545005

辛伐他汀 NB4细胞 细胞增殖 凋亡 NF-κB通路 PCR芯片

2012

苏州大学学报(医学版)
苏州大学

苏州大学学报(医学版)

CSTPCD
影响因子:0.499
ISSN:1673-0399
年,卷(期):2012.32(6)
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