Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 560-182, Republic of Korea.
Mol Med Rep. 2011 Sep-Oct;4(5):879-83. doi: 10.3892/mmr.2011.532. Epub 2011 Jul 5.
Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer pathogenesis. Previously, we reported that the Radix clematidis extract (RCE) inhibits MMP expression by suppressing the nuclear factor-κB (NF-κB) pathway. The purpose of the present study was to investigate the effects of RCE on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The toxicity of RCE was determined by MTT assay. MMP-9 expression was determined by real-time PCR, zymography and Western blot analysis. NF-κB activation was assayed by electrophoretic mobility shift assay (EMSA). Results showed that the expression of MMP-9 and cell invasion in response to TPA was increased, whereas TPA-induced MMP-9 expression and cell invasion was decreased by RCE. Moreover, RCE suppressed NF-κB activation in TPA-treated MCF-7 cells. Thus, RCE is a potent inhibitor of TPA-induced MMP-9 expression and markedly blocks the NF-κB pathway in MCF-7 cells.
基质金属蛋白酶-9（MMP-9）可降解细胞外基质（ECM），在乳腺癌发病机制中发挥重要作用。先前，我们曾报道，威灵仙提取物（RCE）通过抑制核因子-κB（NF-κB）通路抑制 MMP 表达。本研究旨在探讨 RCE 对 MCF-7 细胞中 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的 MMP-9 表达和细胞侵袭的影响。采用 MTT 法测定 RCE 的毒性。通过实时 PCR、酶谱分析和 Western blot 分析测定 MMP-9 的表达。采用电泳迁移率变动分析（EMSA）测定 NF-κB 活化。结果表明，TPA 诱导的 MMP-9 表达和细胞侵袭增加，而 RCE 降低 TPA 诱导的 MMP-9 表达和细胞侵袭。此外，RCE 抑制 TPA 处理的 MCF-7 细胞中 NF-κB 的活化。因此，RCE 是 TPA 诱导的 MMP-9 表达的有效抑制剂，并显著阻断 MCF-7 细胞中的 NF-κB 通路。
