To explore the mechanisms underlying the effect of sodium valproate (VPA) on human promyelocytic leukemia cell line NB4, the genome-wide oligonucleotide microarray is employed to identify the differentially expressed genes in this process, and MAS tool is also used to further analyze the pathways which the regulated genes are involved in. The results show that: 1) the cell growth is inhibited and the expression of differentiation antigen (CDllb) is increased in NB4 cells with 2 mmol·L-1 VPA for 48 h; 2) in this context, there are 1 640 significantly regulated genes (fold changes≥ 2) invovled; 3) these differentially expressed genes participate in many important biological processes, in which cell cycle, amino acid metabolism, DNA repair and MAPK signaling pathway are significantly enriched pathways. Using real-time RT-PCR, this study verified 8 differentially expressed genes identified by microarray, demonstrating these genes are the effect targets of VPA-induced differentiation of NB4 cells.The combination of microarray technique with bioinformatics analysis is a useful way for exploring the molecular mechanism of anticancer drug action.%为了研究丙戊酸钠(Sodium valproate,VPA)诱导早幼粒白血病细胞系NB4分化的作用机制,利用人类全基因组表达谱芯片分析了VPA处理NB4细胞分化后差异表达的基因,并利用MAS等生物信息学工具对芯片结果做了进一步的分析.结果表明,2mmol·L-1VPA处理NB4细胞48 h后,可明显抑制细胞的生长,增加分化抗原(CD11b)的表达;在细胞诱导分化过程中,有1640个基因的表达发生了显著改变(变化倍数≥2);这些差异表达基因参与许多重要的生物学过程,其中,细胞周期、氨基酸代谢、DNA修复和MAPK信号通路是细胞诱导分化过程中显著富集的通路.利用实时荧光定量PCR技术,对芯片筛选到的8个差异表达基因进行了验证,证明这些基因是VPA诱导NB4细胞分化的作用靶点.芯片技术和生物信息学分析工具的联合应用是研究抗肿瘤药物作用机制的有效途径.
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