Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, and Fujioka Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
J Gastroenterol. 2010 Jun;45(6):625-35. doi: 10.1007/s00535-010-0206-8. Epub 2010 Feb 10.
We have indicated previously that long-term feeding of beef tallow increases colorectal cancer in rats. In this study, we investigated the effects of conjugated linoleic acid (CLA) on colon carcinogenesis in rats under long-term feeding of beef tallow diets, pretreated with azoxymethane (AOM).
Six-week-old male Sprague-Dawley rats were fed with 10% beef tallow diet only, 10% beef tallow with 1% CLA in triglyceride form (CLA-TG), or 10% beef tallow with 1% CLA in free fatty acid form (CLA-FFA). Colon carcinogenesis was induced by two intraperitoneal injections of AOM. Aberrant crypt foci (ACFs) were examined at 12 weeks. Cancer, cell proliferation, apoptosis, Wnt signaling, and the arachidonic acid cascade were examined at 44 weeks.
At 12 weeks, CLA-TG and CLA-FFA attenuated the increase in ACFs induced by 10% beef tallow and AOM pretreatment. At 44 weeks, both forms of CLA attenuated multiple colon cancers, and CLA-FFA reduced the incidence of colon cancer to 50% of that seen with CLA-TG. CLA-TG and CLA-FFA decreased the number of 5-bromo-2'-deoxyuridine-positive cells in AOM-pretreated rats fed with 10% beef tallow. CLA-FFA increased the number of apoptotic cells and the activity of caspase-3 in the colon mucosa, and CLA-TG enhanced the activity of caspase-3. Both forms of CLA suppressed Wnt signaling and the arachidonic acid cascade in rats treated with beef tallow and AOM.
These results suggested that CLA-TG and CLA-FFA suppressed colon carcinogenesis in rats with long-term feeding of a 10% beef tallow diet, through several mechanisms. The results of the present study with rats might be applicable to humans.
我们之前曾指出，长期食用牛脂会增加大鼠的结直肠癌风险。在这项研究中，我们研究了共轭亚油酸（CLA）在预先用氧化偶氮甲烷（AOM）处理的大鼠长期食用牛脂饮食下对结肠癌发生的影响。
6 周龄雄性 Sprague-Dawley 大鼠仅喂食 10%牛脂饮食、以三酸甘油酯形式（CLA-TG）添加 1%CLA 的 10%牛脂饮食或以游离脂肪酸形式（CLA-FFA）添加 1%CLA 的 10%牛脂饮食。通过两次腹腔注射 AOM 诱导结肠癌变。在 12 周时检查异常隐窝病灶（ACF）。在 44 周时检查癌症、细胞增殖、细胞凋亡、Wnt 信号和花生四烯酸级联。
在 12 周时，CLA-TG 和 CLA-FFA 减弱了 10%牛脂和 AOM 预处理引起的 ACF 增加。在 44 周时，两种形式的 CLA 均减弱了多发性结肠癌，CLA-FFA 将结肠癌的发生率降低到与 CLA-TG 相同的 50%。CLA-TG 和 CLA-FFA 减少了喂食 10%牛脂的 AOM 预处理大鼠中 5-溴-2'-脱氧尿苷阳性细胞的数量。CLA-FFA 增加了结肠黏膜中细胞凋亡的数量和半胱天冬酶-3 的活性，CLA-TG 增强了半胱天冬酶-3 的活性。两种形式的 CLA 均抑制了牛脂和 AOM 处理大鼠的 Wnt 信号和花生四烯酸级联。
这些结果表明，CLA-TG 和 CLA-FFA 通过多种机制抑制了大鼠长期食用 10%牛脂饮食引起的结肠癌发生。本研究中大鼠的结果可能适用于人类。
