Elimrani Ihsan, Koenekoop Jamie, Dionne Serge, Marcil Valerie, Delvin Edgar, Levy Emile, Seidman Ernest G
a Division of Gastroenterology, Faculty of Medicine, IBD Laboratory, Research Institute, McGill University Health Center, McGill University , Montreal , Quebec , Canada.
b Department of Nutrition and Biochemistry , Sainte Justine Hospital Research Center, University of Montreal , Montreal , Quebec , Canada.
Nutr Cancer. 2017 Feb-Mar;69(2):276-288. doi: 10.1080/01635581.2017.1263346. Epub 2017 Jan 3.
Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2 mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates. Increased histological inflammation score and increased IL-6 were observed in the mucosa of vD-deficient mice. Overall incidence of colonic tumors was not significantly different between vD-deficient and vD-supplemented mice. Higher tumor multiplicity was observed in vD-deficient vs vD-supplemented groups (both mouse strains). After AOM/DSS treatment, decreased plasma 25(OH)D levels and downregulation of vD target genes Cyp24 and Vdr were observed in both mice strains (vD-deficient or vD-supplemented diet), compared to saline-treated controls on the vD-deficient diet. In conclusion, vD supplementation reduced colitis severity and decreased the number of inflammation-associated colorectal tumors in both C57BL/6J and Nod2 mice, independent of NOD2.
炎症性肠病（IBD）患者患结直肠癌（CRC）的风险增加。维生素D（vD）可诱导NOD2基因表达，增强免疫力，而缺乏则会损害肠道上皮完整性，增加炎症。本研究调查了vD对结肠炎中CRC的影响，以及预防益处是否通过NOD2介导。通过用氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）循环（×3）处理C57BL/6J和Nod2小鼠来诱导炎症相关的CRC。与补充vD的小鼠相比，vD缺乏的小鼠表现出更严重的结肠炎，体重减轻更多，结肠炎活动指数更高，结肠重量/长度比增加，生存率更低。在vD缺乏的小鼠黏膜中观察到组织学炎症评分增加和IL-6升高。vD缺乏和补充vD的小鼠结肠肿瘤的总体发生率没有显著差异。在vD缺乏组与补充vD组（两种小鼠品系）中均观察到更高的肿瘤多发性。与vD缺乏饮食的生理盐水处理对照组相比，在两种小鼠品系（vD缺乏或补充vD饮食）中，AOM/DSS处理后均观察到血浆25（OH）D水平降低以及vD靶基因Cyp24和Vdr下调。总之，补充vD可降低C57BL/6J和Nod2小鼠的结肠炎严重程度，并减少炎症相关结直肠肿瘤的数量，且与NOD2无关。
