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水飞蓟宾通过阻断丝裂原活化蛋白激酶(MAPK)信号通路介导的活化蛋白-1(AP-1)激活,抑制佛波酯(PMA)诱导的MCF-7人乳腺癌细胞基质金属蛋白酶-9(MMP-9)的表达。

Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells.

作者信息

Lee Syng-Ook, Jeong Yun-Jeong, Im Hyo Gwon, Kim Cheorl-Ho, Chang Young-Chae, Lee In-Seon

机构信息

Department of Food Science and Technology and The Center for Traditional Microorganism Resources (TMR), Keimyung University, Daegu 704-701, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2007 Mar 2;354(1):165-71. doi: 10.1016/j.bbrc.2006.12.181. Epub 2007 Jan 2.

DOI:10.1016/j.bbrc.2006.12.181
PMID:17214970
Abstract

Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.) on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Silibinin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7. Silibinin has been found to inhibit PMA-induced MMP-9 gene transcriptional activity by blocking the activation of AP-1 via MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that silibinin reduces PMA-induced invasion of MCF-7 cells. These results suggest that silibinin represents a potential anti-metastatic agent suppressing PMA-induced cancer cell invasion through the specific inhibition of AP-1-dependent MMP-9 gene expression.

摘要

基质金属蛋白酶-9(MMP-9)在癌细胞的侵袭和转移中起重要作用。在本研究中,我们检测了水飞蓟宾(一种来自水飞蓟的黄酮类抗氧化剂)对佛波酯(PMA)诱导的MCF-7人乳腺癌细胞中MMP-9表达的抑制作用。水飞蓟宾显著且选择性地抑制了PMA诱导的MCF-7细胞中MMP-9的表达。已发现水飞蓟宾通过阻断丝裂原活化蛋白激酶(MAPK)信号通路激活转录激活因子1(AP-1),从而抑制PMA诱导的MMP-9基因转录活性。此外,基质胶侵袭试验表明,水飞蓟宾可减少PMA诱导的MCF-7细胞侵袭。这些结果表明,水飞蓟宾是一种潜在的抗转移剂,通过特异性抑制AP-1依赖性MMP-9基因表达来抑制PMA诱导的癌细胞侵袭。

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