Hirata Yoshimasa, Nakagawa Takatoshi, Moriwaki Kazumasa, Koubayashi Eiko, Kakimoto Kazuki, Takeuchi Toshihisa, Inoue Takuya, Higuchi Kazuhide, Asahi Michio
Department of Internal Medicine II, Faculty of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Department of Pharmacology, Faculty of Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
J Clin Biochem Nutr. 2018 May;62(3):221-229. doi: 10.3164/jcbn.17-106. Epub 2018 Mar 17.
Colon cancer prevalence is high worldwide. -GlcNAcylation has been associated with tumor growth in various tissues, including the colon; however, its link to carcinogenesis is not fully understood. We investigated the association of -GlcNAcylation with colon carcinogenesis using a 1,2-dimethylhydrazine/dextran sodium sulfate-induced colon carcinogenesis model in wild type and -GlcNAc transferase-transgenic (-Tg) mice. The incidence of colon cancer was significantly lower in -Tg than in wild type mice. The colonic length was not shortened in -Tg mice, and NF-κB p65 phosphorylation was strongly suppressed, indicating that reduction of inflammation might be related to the alleviation of colon carcinogenesis. Dextran sodium sulfate-induced acute colitis mice were used to evaluate the effect of -GlcNAcylation on inflammation at the maximal inflammation period. In -Tg mice, NF-κB p65 phosphorylation and interleukin-1β mRNA expression were suppressed. Histochemical staining demonstrated shedding of colon epithelial cells in wild type mice a few days after dextran sodium sulfate treatment, whereas they remained essentially intact in -Tg mice. There were no significant differences on histochemical staining in the remaining epithelia between groups. These data suggest that -GlcNAcylation could prevent colon carcinogenesis through reducing acute maximum inflammation, suggesting modulation of -GlcNAcylation as a novel therapeutic option.
全球范围内结肠癌的患病率都很高。N-乙酰葡糖胺化与包括结肠在内的各种组织中的肿瘤生长有关；然而，其与致癌作用的联系尚未完全明确。我们使用1,2-二甲基肼/葡聚糖硫酸钠诱导的结肠癌发生模型，在野生型和N-乙酰葡糖胺转移酶转基因（-Tg）小鼠中研究了N-乙酰葡糖胺化与结肠癌发生的关联。-Tg小鼠的结肠癌发病率显著低于野生型小鼠。-Tg小鼠的结肠长度未缩短，且NF-κB p65磷酸化受到强烈抑制，这表明炎症减轻可能与结肠癌发生的缓解有关。使用葡聚糖硫酸钠诱导的急性结肠炎小鼠来评估N-乙酰葡糖胺化在最大炎症期对炎症的影响。在-Tg小鼠中，NF-κB p65磷酸化和白细胞介素-1β mRNA表达受到抑制。组织化学染色显示，葡聚糖硫酸钠处理几天后，野生型小鼠的结肠上皮细胞脱落，而-Tg小鼠的结肠上皮细胞基本保持完整。两组剩余上皮细胞的组织化学染色没有显著差异。这些数据表明，N-乙酰葡糖胺化可以通过减轻急性最大炎症来预防结肠癌发生，这提示调节N-乙酰葡糖胺化可能是一种新的治疗选择。
