Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea.
Carcinogenesis. 2012 Apr;33(4):931-6. doi: 10.1093/carcin/bgs106. Epub 2012 Feb 21.
A close relationship between inflammation and colon cancer has been widely accepted, and interleukin (IL)-17A plays an important role in controlling colonic inflammation. However, the role of IL-17A has not yet been validated in colitis-associated cancer (CAC). This study aims to identify the effects of IL-17A in tumorigenesis utilizing IL-17A-deficient mice in an experimental CAC model. CAC was induced in both the IL-17A-deficient and the C57BL/6 (wild-type, WT) mice by injection of 12.5 mg/kg azoxymethane followed by three rounds of 1.7% dextran sodium sulfate exposure to elicit colitis. On day 63 after the start of the study, mice were sacrificed. Colonic inflammation, proliferation and tumorigenesis were evaluated. Tumor numbers per mouse (1.43 versus 5.80; P = 0.02) and mean tumor size (1.17 versus 3.58 mm; P = 0.01) were significantly decreased in IL-17A-deficient mice compared with WT mice. Furthermore, the inflammation and the proliferation scores of IL-17A-deficient mice were significantly lower than WT mice. In the analysis of inflammatory mediators, IL-6, interferon-γ, tumor necrosis factor-α and IL-17A were markedly decreased in IL-17A-deficient mice compared with WT mice. In the western blot analysis, p-STAT3, cyclin D1, cyclin-dependent kinase 2, cyclin E, Glycogen synthase kinase 3-β and p-Akt were downregulated in IL-17A-deficient mice. Immunohistochemical staining with p-STAT3, Ki-67 and β-catenin revealed lower number of stained cells in IL-17A-deficient mice compared with WT mice. IL-17A ablation significantly decreases CAC tumorigenesis and thus may play an important role associated with chronic colitis.
炎症与结肠癌之间的密切关系已被广泛接受，白细胞介素（IL）-17A 在控制结肠炎症中发挥重要作用。然而，IL-17A 在结肠炎相关癌症（CAC）中的作用尚未得到验证。本研究旨在利用实验性 CAC 模型中的 IL-17A 缺陷小鼠来确定 IL-17A 在肿瘤发生中的作用。通过注射 12.5mg/kg 氧化偶氮甲烷，然后用 1.7%葡聚糖硫酸钠暴露 3 次，在 IL-17A 缺陷和 C57BL/6（野生型，WT）小鼠中诱导 CAC。在研究开始后的第 63 天，处死小鼠。评估结肠炎症、增殖和肿瘤发生情况。与 WT 小鼠相比，IL-17A 缺陷小鼠的肿瘤数量（1.43 与 5.80；P = 0.02）和平均肿瘤大小（1.17 与 3.58mm；P = 0.01）显著降低。此外，IL-17A 缺陷小鼠的炎症和增殖评分明显低于 WT 小鼠。在炎症介质分析中，与 WT 小鼠相比，IL-17A 缺陷小鼠的 IL-6、干扰素-γ、肿瘤坏死因子-α和 IL-17A 明显减少。在 Western blot 分析中，与 WT 小鼠相比，IL-17A 缺陷小鼠的 p-STAT3、细胞周期蛋白 D1、细胞周期蛋白依赖性激酶 2、细胞周期蛋白 E、糖原合酶激酶 3-β 和 p-Akt 下调。与 WT 小鼠相比，IL-17A 缺陷小鼠的 p-STAT3、Ki-67 和 β-连环蛋白免疫组织化学染色显示染色细胞数量减少。IL-17A 缺失显著降低 CAC 肿瘤发生，因此可能在慢性结肠炎相关的肿瘤发生中发挥重要作用。
