水飞蓟素是从菊科药用植物水飞蓟种子的种皮中提取出来的植物提取物，该物质具有如下功效：保护肝脏细胞免受毒性物质侵害，尤其是酒精及环境污染物(农药、重金属等)入侵损害肝脏；具有强力的抗氧化功能，能保护肝脏细胞免受自由基破坏，效力远胜于维生素E；促进蛋白质的合成，加快制造新的肝脏细胞，或令已受损的肝脏细胞自行修复。因此被称为“天然的保肝药”。
另外水飞蓟素具有抗辐射、抗衰老、防治动脉硬化、延缓皮肤老化等功效。近来，一些研究还发现水飞蓟宾具有癌症治疗和化学预防作用，相关功效已经在体外和体内模型上得到了验证。
低密度脂蛋白受体相关蛋白6（LRP6）是必不可少的Wnt/β-catenin信号途径中Wnt信号受体，是非常有前途的癌症预防和治疗靶标。最新研究发现，水飞蓟宾能抑制内源性LRP6的表达，阻断WNT3A诱导的LRP6磷酸化和HEK293细胞中Wnt/β-catenin信号通路的活化。
重要的是，研究人员还证实水飞蓟宾也能够前列腺癌PC-3、DU-145细胞和乳腺癌细胞MDA-MB-231、T-47D细胞中内源性LRP6的表达和磷酸化，阻断Wnt /β-catenin信号。
其中机制为水飞蓟宾抑制LRP6的启动子活性，降低前列腺癌和乳腺癌细胞中LRP6的mRNA水平。总之研究数据表明，水飞蓟宾是一种新型的小分子阻断Wnt /β-catenin信号的抑制剂，其中机制就是通过在转录水平抑制Wnt信号受体LRP6的表达，发挥抗肿瘤活性。（生物谷：Bioon.com）
doi:10.1016/j.cellsig.2012.07.009
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Silibinin Inhibits Wnt/β-catenin Signaling by Suppressing Wnt Co-receptor LRP6 Expression in Human Prostate and Breast Cancer Cells.
Lu W, Lin C, King TD, Chen H, Reynolds RC, Li Y.
Silibinin is a natural compound isolated from milk thistle seed extracts, and has traditionally been used as a hepatoprotectant. A number of studies have also established the cancer therapeutic and chemopreventive role of silibinin in both in vitro and in vivo models. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for the Wnt/β-catenin pathway and represents a promising target for cancer prevention and therapy. In the present study, we found that silibinin was able to repress endogenous LRP6 expression and block Wnt3A-induced LRP6 phosphorylation and Wnt/β-catenin signaling activation in HEK293 cells. Importantly, silibinin was also able to suppress endogenous LRP6 expression and phosphorylation and block Wnt/β-catenin signaling in prostate cancer PC-3 and DU-145 cells and breast cancer MDA-MB-231 and T-47D cells. Mechanistically, silibinin inhibited LRP6 promoter activity and decreased LRP6 mRNA levels in prostate and breast cancer cells. Finally, we demonstrated that silibinin displayed anticancer activity with IC(50) values comparable to those shown to suppress LRP6 expression and Wnt/β-catenin signaling activities in prostate and breast cancer cells. Our data indicate that silibinin is a novel small molecule Wnt/β-catenin signaling inhibitor by suppressing Wnt co-receptor LRP6 expression at the transcription level, and that the anti-cancer activity of silibinin is associated with its inhibitory effect on Wnt/LRP6 signaling.
