Nowak Johannes, Weylandt Karsten H, Habbel Piet, Wang Jingdong, Dignass Axel, Glickman Jonathan N, Kang Jing X
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Carcinogenesis. 2007 Sep;28(9):1991-5. doi: 10.1093/carcin/bgm166. Epub 2007 Jul 18.
Colorectal cancer (CRC) is the second leading cause of cancer deaths in USA. Anti-inflammatory drugs were shown to be effective in the prevention of CRC, supporting a link between inflammation and tumorigenesis in the colon. However, due to their side effects, long-term administration of these drugs for CRC prevention is not feasible. An increased tissue content of omega-3 polyunsaturated fatty acids (n-3 PUFA) can dampen colon inflammation in animals as well as in humans. Whether increasing colon tissue n-3 PUFA alone is effective in preventing colon tumorigenesis remains to be investigated. Here we show that endogenously increased tissue levels of n-3 PUFA in the fat-1 transgenic mouse model lower incidence and growth rate of colon tumors induced by inflammation (dextrane sodium sulfate) plus treatment with carcinogen (azoxymethane). This was accompanied by lower activity of nuclear factor kappa B (NF-kappaB), higher expression of transforming growth factor beta in the colons and lower expression of inducible nitric oxide synthase in the tumors of fat-1 animals. Our data provide new insight into the mechanism by which n-3 PUFA suppresses tumorigenesis through dampening of inflammation and NF-kappaB activity. These results support a protective role of n-3 PUFA supplementation in the prevention of CRC.
结直肠癌（CRC）是美国癌症死亡的第二大主要原因。抗炎药物已被证明在预防结直肠癌方面有效，这支持了炎症与结肠肿瘤发生之间的联系。然而，由于其副作用，长期服用这些药物来预防结直肠癌是不可行的。ω-3多不饱和脂肪酸（n-3 PUFA）组织含量的增加可以减轻动物和人类的结肠炎症。仅增加结肠组织中的n-3 PUFA是否能有效预防结肠肿瘤发生仍有待研究。在此我们表明，在fat-1转基因小鼠模型中，内源性增加的组织n-3 PUFA水平降低了由炎症（葡聚糖硫酸钠）加致癌物（氧化偶氮甲烷）诱导的结肠肿瘤的发生率和生长速率。这伴随着fat-1动物结肠中核因子κB（NF-κB）活性降低、转化生长因子β表达升高以及肿瘤中诱导型一氧化氮合酶表达降低。我们的数据为n-3 PUFA通过减轻炎症和NF-κB活性抑制肿瘤发生的机制提供了新的见解。这些结果支持了补充n-3 PUFA在预防结直肠癌中的保护作用。
