Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an 710061, PR China.
Oncol Rep. 2010 Jun;23(6):1545-52.
Silibinin, a naturally occurring flavanone isolated from milk thistle extract, has been shown to possess strong anticancer efficacy against both androgen-dependent and androgen-independent prostate cancer, wherein it inhibits not only cell growth, but also cell invasion and metastasis. Inhibitory effects of silibinin on prostate cancer invasion, motility and migration were previously observed in the highly bone metastatic ARCaP M cell line; however, mechanisms of such efficacy are not completely elucidated. The epithelial-to-mesenchymal transition (EMT) is a crucial step in the progression of prostate cancer, reversal or inhibition of EMT by drugs thus provides a new approach to prostate cancer therapy. In the present study, we found that silibinin treatment resulted in the up-regulation of cytokeratin-18 and down-regulation of vimentin and MMP2, which was consistent with morphologic reversal of EMT phenotype leading to be epithelial. Moreover, we found that silibinin could inhibit the nuclear factor kappaB (NF-kappaB) p50 translocation via the up-regulation of I kappaB alpha protein, and possibly subsequently down-regulated the expression of two major EMT regulators, ZEB1 and SLUG transcription factors. Overall these findings demonstrate silibinin was able to reverse EMT to suppress the invasive property of metastatic prostate cancer cells at the transcriptional level.
水飞蓟宾，一种从奶蓟草提取物中分离出来的天然黄酮类化合物，已被证明对雄激素依赖性和非依赖性前列腺癌均具有强大的抗癌功效，它不仅能抑制细胞生长，还能抑制细胞侵袭和转移。先前在高骨转移性 ARCaP M 细胞系中观察到水飞蓟宾对前列腺癌侵袭、运动和迁移的抑制作用；然而，其疗效的机制尚未完全阐明。上皮间质转化（EMT）是前列腺癌进展的关键步骤，因此药物对 EMT 的逆转或抑制为前列腺癌治疗提供了一种新方法。在本研究中，我们发现水飞蓟宾治疗导致细胞角蛋白-18 的上调和波形蛋白和 MMP2 的下调，这与 EMT 表型的形态逆转导致上皮细胞一致。此外，我们发现水飞蓟宾可以通过上调 I kappaB alpha 蛋白抑制核因子 kappaB（NF-kappaB）p50 易位，可能随后下调两个主要 EMT 调节剂 ZEB1 和 SLUG 转录因子的表达。总的来说，这些发现表明水飞蓟宾能够逆转 EMT，从而在转录水平上抑制转移性前列腺癌细胞的侵袭特性。
