Suppression of tumorigenesis in the Apcmin mouse:: down-regulation of β-catenin signaling by a combination of tea plus sulindac
Suppression of tumorigenesis in the Apcmin mouse:: down-regulation of β-catenin signaling by a combination of tea plus sulindac
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DOI：
10.1093/carcin/24.2.263
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发表时间：
2003-02-01
期刊：
影响因子：
4.7
通讯作者：
Dashwood, RH
中科院分区：
文献类型：
--
作者：
Orner, GA;Dashwood, WM;Dashwood, RH
流行病学和动物研究表明，茶可能对胃肠道癌症有保护作用。白茶是加工最少的茶形式，含有高水平的多酚，像绿茶一样，对杂环胺引发的雄性F344大鼠结肠异常隐窝形成具有化学预防作用。我们首次检测了白茶和绿茶对C57BL/6J-APC(Min/+)(APC(Min))小鼠肠道肿瘤形成的抑制作用。每种茶还与舒林酸进行了比较，舒林酸是一种已知的对APC(MIN)小鼠非常有效的非类固醇消炎药。雄性C57BL/6J(+/+)(野生型)和APC(Min)小鼠在饮水中加入白茶或绿茶(1.5%w/v，冲泡时间2分钟)，每晚80只。舒林酸，晚上80点的组合。在1.5%白茶或pH缓冲水中加入舒林酸。治疗12周后，服用白茶、绿茶或舒林酸的APC(Min)小鼠的肿瘤显著少于对照组(P<；0.05)。1.5%的绿茶或白茶提供的保护与晚上80%提供的保护相当。舒林酸。白茶加舒林酸联合治疗的小鼠比单独治疗的小鼠肿瘤显著减少(P<；0.05)。β-连环素和β-连环素/Tcf-4调节蛋白Cyclin D-1和c-jun很容易在息肉中检测到，但在TEA和舒林酸处理的小鼠正常肠道中显著减少。这项研究提供的证据表明，茶，特别是当与舒林酸联合使用时，通过直接或间接影响β-连环素/APC途径，对雄性APC(MIN)小鼠的肠道肿瘤具有非常有效的抑制作用。
Epidemiological and animal studies suggest that tea may be protective towards cancers of the GI tract. White tea, the least processed form of tea, contains high levels of polyphenols and, like green tea, is chemopreventive towards heterocyclic amine-initiated colonic aberrant crypt formation in male F344 rats. We examined for the first time the relative effectiveness of white and green tea in suppressing intestinal tumorigenesis in C57BL/6J-Apc(Min/+) (Apc(min)) mice. Each tea was also compared with sulindac, a nonsteroidal anti-inflammatory drug known to be highly effective in Apc(min) mice. Male C57BL/6J (+/+) (wild-type) and Apc(min) mice were treated in the drinking water with white tea or green tea (1.5% w/v, 2 min brew-time), 80 p.p.m. sulindac, a combination of 80 p.p.m. sulindac in 1.5% white tea, or pH buffered water. After 12 weeks of treatment, Apc(min) mice given white tea, green tea, or sulindac had significantly fewer tumors than controls (P < 0.05). The protection provided by 1.5% green or white tea was comparable to that provided by 80 p.p.m. sulindac. Mice treated with a combination of white tea plus sulindac had significantly fewer tumors than either treatment alone (P < 0.05). beta-catenin and beta-catenin/Tcf-4 regulated proteins Cyclin D-1 and c-Jun were readily detected in polyps, but markedly reduced in normal-looking intestines of mice treated with both tea and sulindac. This research provides evidence that teas, particularly when administered in combination with sulindac, are highly effective at inhibiting intestinal neoplasia in male Apc(min) mice via direct or indirect effects on the beta-catenin/APC pathway.