Suppression of azoxymethane-induced colon cancer development in rats by dietary resistant starch
Suppression of azoxymethane-induced colon cancer development in rats by dietary resistant starch
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DOI：
10.4161/cbt.6.10.4764
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发表时间：
2007-10-01
影响因子：
3.6
通讯作者：
Young, Graerne P.
中科院分区：
文献类型：
--
作者：
Le Leu, Richard K.;Brown, Ian L.;Young, Graerne P.
抗性淀粉是一种复合碳水化合物，到达结肠后可被结肠微生物群发酵，产生短链脂肪酸 (SCFA)，特别是丁酸盐。 RS 对结直肠肿瘤发生的影响是截然不同的，其保护作用仍存在争议。丁酸盐作为结肠细胞增殖、分化和凋亡的首选代谢燃料和调节剂具有重要作用，并可能在癌症预防中发挥作用。因此，不同底物产生的丁酸盐的差异可以解释 RS 效果的差异。这项研究评估了这样的假设：饲喂膳食抗性淀粉（如高直链淀粉玉米淀粉）可以防止氧化偶氮甲烷（AOM）结肠癌发生，并对结肠腔环境产生有利影响。雄性 Sprague-Dawley 大鼠 (n = 90) 接受三种饮食之一：对照（不添加膳食纤维或 RS）、10% HAS（含有 100 g/kg 生高直链玉米淀粉）或 20% HAS（含有 200 g/kg 高直链淀粉玉米淀粉）。给大鼠喂食实验饮食四个星期，然后在第五周和第六周注射 AOM（15 毫克/千克）。切除结肠（第二次注射后25周）以评估肿瘤形成、细胞凋亡、增殖细胞核抗原（PCNA）标记指数和短链脂肪酸水平。与对照饮食相比，饲喂抗性淀粉显着降低了结肠腺癌的发病率（p < 0.01）和多重性（p < 0.05）。两种剂量的 HAS 都对结肠肿瘤发生产生类似的保护作用。饲喂 RS 显着增加了总 SCFA 浓度，包括远端结肠中的丁酸盐。在饲喂抗性淀粉的远端结肠中，细胞凋亡（p < 0.01）也增强，而 PCNA 标记指数降低（p < 0.01）。食用RS作为膳食高直链淀粉玉米淀粉对结肠癌发展的保护作用似乎与结肠中的活跃发酵有关，特别是通过丁酸的产生。
Resistant starch is a complex carbohydrate that reaches the colon where it can be fermented by the colonic microflora resulting in production of short chain fatty acids (SCFA), in particular butyrate. RS effects on colorectal tumorigenesis are contrasting and protection remains controversial. Butyrate has an important role as the preferred metabolic fuel and regulator of colonocyte proliferation, differentiation and apoptosis and may play a role in cancer prevention. Thus variation in butyrate production from different substrates might explain the variation in effect of RS. This study evaluated the hypothesis that feeding dietary resistant starch (as high amylose maize starch) would protect against azoxymethane (AOM)-colon carcinogenesis and favorably influence the colonic luminal environment. Male Sprague-Dawley rats (n = 90) were provided one of three diets: Control (without added dietary fibre or RS), 10% HAS (contained 100 g/kg raw high amylose maize starch) or 20% HAS (contained 200 g/kg high amylose maize starch). Rats were fed their experimental diets for four weeks after which they were injected with AOM (15 mg/kg) during the fifth and six week. Colons were resected (25 weeks post second injection) for evaluation of tumor formation, apoptosis, proliferating cell nuclear antigen (PCNA) labelling index and short chain fatty acid levels. Feeding resistant starch significantly reduced the incidence (p < 0.01) and multiplicity (p < 0.05) of adenocarcinomas in the colon compared to the Control diet. Both doses of HAS resulted in similar protection against colon tumorigenesis. Feeding RS significantly increased total SCFA concentrations, including butyrate in-the distal colon. Apoptosis (p < 0.01) was also enhanced while PCNA labelling index was reduced (p < 0.01) in the distal colon with resistant starch feeding. The protective effect of consumption of RS as dietary high-amylose cornstarch against colon cancer development appears to be related to active fermentation in the colon, particularly through production of butyrate.