The mechanism of silibinin inhibits cancer cell migrarion/invasion

• Main Authors: Pei Ni Chen, 陳霈霓
• Other Authors: 謝易修
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/44339494816356174059

碩士 === 中山醫學大學 === 生物化學研究所 === 91 === Silibinin is a flavonoid antioxidant extracted from milk thistle. It was used as a liver detoxicant previously. In recent studies, silibinin has shown its anti-carcinogenesis property. In order to observe the effect of silibinin to cancer cells metastasis in vitro. we chosed a high metastasis human lung cancer cell line : A549 cells treated with various concentration of silibinin to probe into the potential of inhibiting cancer cells invasion. Tumor metastasis are multifaceted processes that mainly involve proteolytic degradation of the extracellular matrix, changes cell-matrix adhesion, and regulate cell motility. In the first, we found that silibinin inhibited A549 cells invasion via modified Boyden chamber invasion assay and both of MMP-2 and its activator：uPA activity were also inhibited by silibinin via gelatin zymography and casein zymography assay. In the other side, silibinin also inhibited A549 cells motility and cell-matrix adhesion by Boyden chamber assay and cell-matrix adhesion assay. In the signal transduction pathway, we found Akt, ERK1/2 and p38 phosphorylation and NF-kB protein level were inhibited by silibinin via western blotting. In order to confirm the activation of above proteins whether regulate A549 invasion ability, we used specific inhibitors：LY294002, SB253080 and U0126 to clearified that PI-3K and p38 signaling regulate MMP-2 expression, cell motility and cell invasion of A549, and MEK signaling regulate MMP-2, u-PA expression and cell invasion.