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安农西亚红苹果多酚提取物经口灌胃干预 ApcMin/+ 小鼠两种饮食致肠息肉的实验研究

Chemoprevention of intestinal polyps in ApcMin/+ mice fed with western or balanced diets by drinking annurca apple polyphenol extract.

机构信息

Department of Internal Medicine, Baylor Research Institute, Sammons Cancer Center, USA.

出版信息

Cancer Prev Res (Phila). 2011 Jun;4(6):907-15. doi: 10.1158/1940-6207.CAPR-10-0359. Epub 2011 Mar 7.

Abstract

The Western diet (WD) is associated with a higher incidence of colorectal cancer (CRC) than the Mediterranean diet. Polyphenols extracted from Annurca apple showed chemopreventive properties in CRC cells. A multifactorial, four-arm study by using wild-type (wt) and Apc(Min/+) mice was carried out to evaluate the effect on polyp number and growth of APE treatment (60 μmol/L) ad libitum in drinking water combined with a WD or a balanced diet (BD) for 12 weeks. Compared with APE treatment, we found a significant drop in body weight (P < 0.0001), severe rectal bleeding (P = 0.0076), presence of extraintestinal tumors, and poorer activity status (P = 0.0034) in water-drinking Apc(Min/+) mice, more remarkably in the WD arm. In the BD and WD groups, APE reduced polyp number (35% and 42%, respectively, P < 0.001) and growth (60% and 52%, respectively, P < 0.0001) in both colon and small intestine. Increased antioxidant activity was found in wt animals fed both diets and in Apc(Min/+) mice fed WD and drinking APE. Reduced lipid peroxidation was found in Apc(Min/+) mice drinking APE fed both diets and in wt mice fed WD. In normal mucosa, mice drinking water had lower global levels of DNA methylation than mice drinking APE. APE treatment is highly effective in reducing polyps in Apc(Min/+) mice and supports the concept that a mixture of phytochemicals, as they are naturally present in foods, represent a plausible chemopreventive agent for CRC, particularly in populations at high risk for colorectal neoplasia.

摘要

西方饮食(WD)与结直肠癌(CRC)的发病率较高有关,而地中海饮食则较低。从安努卡苹果中提取的多酚在 CRC 细胞中显示出化学预防特性。使用野生型(wt)和 Apc(Min / +)小鼠进行了多因素、四臂研究,以评估在饮用水中添加 APE(60 μmol / L)自由摄取并结合 WD 或平衡饮食(BD)12 周对息肉数量和生长的影响。与 APE 治疗相比,我们发现饮水 Apc(Min / +)小鼠的体重明显下降(P <0.0001),严重直肠出血(P = 0.0076),存在肠外肿瘤,活动状态较差(P = 0.0034),在 WD 臂中更为明显。在 BD 和 WD 组中,APE 减少了结肠和小肠中的息肉数量(分别减少 35%和 42%,P <0.001)和生长(分别减少 60%和 52%,P <0.0001)。在两种饮食喂养的 wt 动物和 WD 饮食喂养并饮用 APE 的 Apc(Min / +)小鼠中发现抗氧化活性增加。在两种饮食喂养的 Apc(Min / +)小鼠和 WD 饮食喂养的 wt 小鼠中发现脂质过氧化减少。在饮用 APE 的小鼠的正常黏膜中,DNA 甲基化的总体水平低于饮用饮用水的小鼠。APE 治疗在减少 Apc(Min / +)小鼠中的息肉方面非常有效,并支持这样的概念,即植物化学物质的混合物,如它们在食物中自然存在,代表 CRC 的一种合理的化学预防剂,特别是在结直肠肿瘤高风险人群中。

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