Cancer Research Center, Xiamen University Medical College, Xiamen, China; School of life Science, Xiamen University, Xiamen, China.
J Cell Mol Med. 2013 Nov;17(11):1484-93. doi: 10.1111/jcmm.12119. Epub 2013 Sep 9.
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.
作为一种传统的抗炎中草药，小檗碱最近被报道具有广谱抗肿瘤作用。然而，其作用机制在很大程度上尚不清楚。基因芯片阵列揭示，用小檗碱处理后，Wnt 通路的靶基因 c-Myc 的表达水平降低了 5.3 倍，表明小檗碱可能抑制 Wnt 信号。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 基因的表达和稳定 APC-β-连环蛋白复合物，阻止β-连环蛋白向细胞核内转移。在 ApcMin/+ 小鼠中给予小檗碱治疗，可使肠道内的息肉数量减少、体积减小，同时还可降低 cyclin D1 和 c-Myc 的表达水平。在临床实践中，口服小檗碱也可显著减小家族性腺瘤性息肉病患者的息肉大小，同时抑制息肉样本中 cyclin D1 的表达。这些观察结果表明，小檗碱通过抑制 Wnt/β-连环蛋白信号通路抑制结肠肿瘤的形成，小檗碱可能是预防结肠癌的一种很有前途的药物。
