Department of Oncology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Carcinogenesis. 2013 Jul;34(7):1593-600. doi: 10.1093/carcin/bgt088. Epub 2013 Mar 7.
Chronic colonic inflammation is a known risk factor for colorectal cancer (CRC). Glutamine (GLN) supplementation has shown its anti-inflammation benefit in experimental colitis. Whether GLN is effective in preventing colon carcinogenesis remains to be investigated. The chemopreventive activity of GLN was evaluated in the mouse model of dextran sulfate sodium (DSS)/azoxymethane (AOM)-induced colitis-associated CRC in this study. Mice were treated with DSS/AOM and randomized to receive either a control diet or GLN-enriched diet intermittently of the study. The disease activity index was evaluated weekly. On day 80 of the experiment, the entire colon and rectum were processed for histopathologic examination and further evaluation. Pro-inflammatory mediators and cytokines were measured by enzyme-linked immunosorbent assay, real-time-PCR and western blot analysis. Here, we show that after GLN-enriched diet, the colitis presented a statistical improvement and tumors burden decreased significantly. This was accompanied by lower activity of nuclear factor-κB (NF-κB), decreased expression of cyclooxygenase-2 and inducible nitric oxide synthase, lower expression of cytokines and chemokines as well as reduced proliferation and induced apoptosis in the colons of colitis-associated CRC mice. Our data demonstrate the protective/preventive effect of GLN in the progression of colitis-associated CRC, which was correlated with a dampening of inflammation and NF-κB activity and with a decrease of inflammatory protein overexpression.
慢性结肠炎症是结直肠癌（CRC）的已知风险因素。谷氨酰胺（GLN）补充已显示出其在实验性结肠炎中的抗炎益处。GLN 是否有效预防结肠癌发生仍有待研究。本研究在葡聚糖硫酸钠（DSS）/氧化偶氮甲烷（AOM）诱导的结肠炎相关 CRC 小鼠模型中评估了 GLN 的化学预防活性。小鼠接受 DSS/AOM 处理，并随机分为接受对照饮食或 GLN 富集饮食的实验组。每周评估疾病活动指数。在实验的第 80 天，对整个结肠和直肠进行组织病理学检查和进一步评估。通过酶联免疫吸附试验、实时 PCR 和 Western blot 分析测量促炎介质和细胞因子。在这里，我们表明，在 GLN 富集饮食后，结肠炎的统计学改善和肿瘤负担显著降低。这伴随着核因子-κB（NF-κB）活性降低、环氧化酶-2 和诱导型一氧化氮合酶表达降低、细胞因子和趋化因子表达降低以及结肠炎相关 CRC 小鼠结肠中增殖减少和诱导细胞凋亡。我们的数据表明 GLN 在结肠炎相关 CRC 进展中的保护/预防作用，这与炎症和 NF-κB 活性的抑制以及炎症蛋白过表达的减少有关。
