a Department of Gastroenterology and Hepatology, Renji Hospital, School of Medicine , Shanghai Jiao-Tong University , Shanghai , China.
Nutr Cancer. 2013;65(8):1171-83. doi: 10.1080/01635581.2013.828087. Epub 2013 Oct 7.
The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The objective of this study was to identify potential target genes of butyrate in 1,2-dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR. Data was further analyzed by KEGG, gene ontology (GO), and pathway studio software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and 90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH treatment while upregulated by butyrate, and 475 genes upregulated by DMH while downregulated by butyrate. The results revealed that most of the tumor-related signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF pathway) were downregulated by butyrate. The GO terms related to cell differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and cell migration were significantly affected. The chemopreventive effects of butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms encompassing multiple pathways and GO terms are involved in the regulation of gene expression.
丁酸盐预防结直肠癌（CRC）的机制尚不清楚。本研究的目的是鉴定 1,2-二甲基肼（DMH）诱导的 CRC 小鼠中丁酸盐的潜在靶基因。DMH+丁酸盐、DMH 和对照组小鼠的非肿瘤结直肠组织在安捷伦小鼠全基因组 44K 寡核苷酸微阵列上杂交。通过 qRT-PCR 验证了选定的基因。通过 KEGG、基因本体论（GO）和通路工作室软件进一步分析数据。DMH+丁酸盐组和 DMH 组的肿瘤发生率分别为 30%和 90%（P<0.05）。DMH 处理导致 355 个基因下调，而丁酸盐使其上调，DMH 处理导致 475 个基因上调，而丁酸盐使其下调。结果表明，大多数与肿瘤相关的信号通路（如 MAPK 通路、Wnt 通路、胰岛素通路和 VEGF 通路）被丁酸盐下调。与细胞分化、细胞周期、细胞增殖、细胞死亡、细胞黏附和细胞迁移相关的 GO 术语受到显著影响。丁酸盐在 DMH 诱导的 CRC 小鼠模型中具有化学预防作用。并且涉及多个通路和 GO 术语的机制参与了基因表达的调控。
