Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-gu, Seoul 135-710, South Korea.
J Ethnopharmacol. 2009 Nov 12;126(2):252-7. doi: 10.1016/j.jep.2009.08.032. Epub 2009 Aug 26.
The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway.
Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231.
The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway.
The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK 1/2 inhibitor).
Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.
基质金属蛋白酶-9（MMP-9）和环氧化酶-2（COX-2）的表达是乳腺癌发病机制中的关键步骤。在之前的研究中，我们报道了水飞蓟宾通过 Raf/MEK/ERK 通路抑制 TPA 诱导的 MMP-9 表达。
本文旨在确定 MMP-9 和 COX-2 之间的相关性，以及水飞蓟宾对 TPA 诱导的 MMP-9 和 COX-2 在人乳腺癌细胞 MCF-7 和 MDA-MB231 中的表达的影响。
通过快速细胞增殖试剂盒 II 评估水飞蓟宾的毒性。通过明胶酶谱法和 Western blot 分别分析 MMP-9 和 COX-2 的表达。使用腺病毒组成型激活（CA）-MEK 激活 MEK/ERK 通路。
TPA 诱导 MMP-9 和 COX-2 的表达增加，而水飞蓟宾则降低了 TPA 诱导的 MMP-9 和 COX-2 的表达。我们的结果表明，TPA 诱导的 MMP-9 表达被塞来昔布呈剂量依赖性抑制，但不抑制 MMP-1 的表达。CA-MEK 的过表达显著增加了 MMP-9 和 COX-2 的表达。相反，UO126（MEK1/2 抑制剂）降低了 TPA 诱导的 MMP-9 和 COX-2 的表达。
水飞蓟宾通过抑制乳腺癌细胞中 COX-2 的表达下调 TPA 诱导的 MMP-9 表达。
