Chemoprevention of intestinal tumorigenesis by the natural dietary flavonoid myricetin in APCMin/+ mice.
Chemoprevention of intestinal tumorigenesis by the natural dietary flavonoid myricetin in APCMin/+ mice.
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天然膳食类黄酮杨梅素对 APCMin 小鼠肠道肿瘤发生的化学预防作用
DOI：
10.18632/oncotarget.11108
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Qu XJ
中科院分区：
文献类型：
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作者：
Li Y;Cui SX;Sun SY;Shi WN;Song ZY;Wang SQ;Yu XF;Gao ZH;Qu XJ
杨梅素是一种天然的膳食类黄酮化合物。我们评估了杨梅素对腺瘤性结肠息肉病多发性肠肿瘤（APCMin/+）小鼠肠肿瘤发生的疗效。口服杨梅素，每日1次，连续12周。喂食杨梅素的APCMin/+小鼠产生更少更小的息肉，没有任何不良反应。组织学分析显示每个息肉中异型增生细胞的数量和异型增生的程度减少。免疫组化和蛋白质印迹分析显示，杨梅素选择性抑制细胞增殖，并诱导腺瘤性息肉细胞凋亡。杨梅素的作用与GSK-3β和Wnt/β-catenin通路的调节有关。ELISA分析显示血液中促炎细胞因子IL-6和PGE 2的浓度降低，其在APCMin/+小鼠中升高。杨梅素治疗的效果在起源于结肠的腺瘤性息肉中更为突出。进一步研究表明，杨梅素下调磷酸化p38 MAPK/Akt/mTOR信号通路，这可能是杨梅素抑制腺瘤性息肉的机制之一。总之，我们的数据表明，杨梅素通过一系列生物活性抑制肠道肿瘤发生。鉴于这些结果，我们建议杨梅素可以用于预防，以降低患结肠癌的风险。
Myricetin is a natural dietary flavonoid compound. We evaluated the efficacy of myricetin against intestinal tumorigenesis in adenomatous polyposis coli multiple intestinal neoplasia (APCMin/+) mice. Myricetin was given orally once a day for 12 consecutive weeks. APCMin/+ mice fed with myricetin developed fewer and smaller polyps without any adverse effects. Histopathological analysis showed a decreased number of dysplastic cells and degree of dysplasia in each polyp. Immunohistochemical and western blot analysis revealed that myricetin selectively inhibits cell proliferation and induces apoptosis in adenomatous polyps. The effects of myricetin were associated with a modulation the GSK-3β and Wnt/β-catenin pathways. ELISA analysis showed a reduced concentration of pro-inflammatory cytokines IL-6 and PGE2 in blood, which were elevated in APCMin/+ mice. The effect of myricetin treatment was more prominent in the adenomatous polyps originating in the colon. Further studies showed that myricetin downregulates the phosphorylated p38 MAPK/Akt/mTOR signaling pathways, which may be the mechanisms for the inhibition of adenomatous polyps by myricetin. Taken together, our data show that myricetin inhibits intestinal tumorigenesis through a collection of biological activities. Given these results, we suggest that myricetin could be used preventatively to reduce the risk of developing colon cancers.