丙戊酸钠逆转Kasumi-1白血病细胞株AML1-ETO融合蛋白转录抑制的作用  

Reversed Effect of Valproic Acid on Transcription Inhibition of AML1-ETO Fusion Protein of Kasumi-1 Leukemic Cell Line

作　　者：赵蕾[1] 朱翠敏[1] 张志华[1] 田文亮[1] 郝长来[1] 

机构地区：[1]承德医学院附属医院血液病科,河北承德067000

出　　处：《中国实验血液学杂志》2009年第2期363-367,共5页Journal of Experimental Hematology

基　　金：河北省自然科学基金;编号C2008000660

摘　　要：本研究探讨组蛋白脱乙酰化酶抑制剂(HDAC)丙戊酸钠(VPA)逆转Kasumi-1白血病细胞株AML1-ETO融合蛋白转录抑制机制的作用。Kasumi-1细胞经不同浓度VPA处理不同时间,采用半定量RT-PCR分析AML1-ETO、AML1及cyclin D2mRNA水平的变化情况。结果表明:不同浓度VPA处理Kasumi-1不同时间,AML1-ETOmRNA水平无明显变化;1-3mmol/LVPA处理Kasumi-1细胞3天时,与对照组比较,AML1mRNA表达水平增高,呈现剂量依赖性,差别具有统计学意义。以3mmol/L VPA处理Kasumi-1细胞,与对照组比较,3mmol/L VPA组cyclin D2mRNA表达水平降低;以不同浓度VPA处理Kasumi-1细胞3天,结果发现随着VPA药物浓度加大cyclinD2mRNA表达水平降低,呈现剂量依赖性,差别具有统计学意义。结论:VPA能通过抑制HDAC的活性,消除AML1/ETO融合蛋白的转录抑制并增加aml-1基因转录,下调aml-1靶基因cyclin D2mRNA的表达。This study was aimed to investigate the mechanism of histone deacetylase （HDAC） inhibitor, valproic acid （ VPA）, reversing transcription inhibition of AML1-ETO fusion protein in Kasumi-1 cell line. The mRNA expres- sions of AML1-ETO, AML1 and cyclin D2 were detected by semi-quantitation RT-PCR after treating kasumi-1 cells with VPA at different doses/and different time points. The results indicated that the mRNA expression of AML1-ETO showed no obvious change, when kasumi-1 cells were treated with VPA. Compared with control group, the expression level of AML1 mRNA signifiantly increased in a dose-dependent manner. Compared with control group, the expression level of cyclin D2 mRNA significantly decreased when kasumi-1 cells had been treated with 3 mmol/L VPA as well as kasumi-1 cells were treated with different concentrations of VPA for 3 days. In conclusion, VPA could remove transcription inhibition of AML1-ETO fusion protein, increase transcription of AML1 and down-regulate mRNA expression of AML1 target gene cyclin D2 through HDAC inhibiting activity.

关 键 词：组蛋白脱乙酰化酶 丙戊酸钠 Kasumi-1细胞株 AML1-ETO 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]