Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling.
Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling.
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小檗碱通过抑制 Wnt 信号传导，有效减弱 ApcMin 小鼠和家族性腺瘤性息肉病患者的肠息肉生长
DOI：
10.1111/jcmm.12119
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发表时间：
2013-11
影响因子：
5.3
通讯作者：
Hu T
中科院分区：
文献类型：
--
作者：
Zhang J;Cao H;Zhang B;Cao H;Xu X;Ruan H;Yi T;Tan L;Qu R;Song G;Wang B;Hu T
小檗碱是一种传统的抗炎中草药，近年来研究发现其具有广泛的抗肿瘤作用。然而，其机制在很大程度上是未知的。基因芯片结果显示，小檗碱作用后，Wnt信号通路的靶基因c-Myc表达下调5.3倍，表明小檗碱可能抑制Wnt信号通路。TOPflash分析显示，小檗碱处理后Wnt活性显著降低，其机制可能是小檗碱通过上调APC基因表达，稳定APC-β-catenin复合物，阻断β-catenin向细胞核的转移。在ApcMin/+小鼠中给予小檗碱后，肠内息肉更少更小，沿着细胞周期蛋白D1和c-Myc表达减少。在临床实践中，口服黄连素还可显著减小家族性腺瘤性息肉病患者的息肉大小，同时沿着息肉样品中细胞周期蛋白D1表达的抑制。这些观察结果表明，小檗碱通过抑制Wnt/β-catenin信号传导抑制结肠肿瘤的形成，并且小檗碱可能是预防结肠癌的有希望的药物。
As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer.
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影响因子：
4.5
作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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