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首页> 外文期刊>Life sciences >Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.
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Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.

机译：表没食子儿茶素-3-没食子酸酯（EGCG）在下调人乳腺癌细胞MCF-7中的明胶酶-A（MMP-2）的多功能作用。

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AIMS: The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7. MAIN METHODS: MCF-7 was treated with EGCG (20 muM, 24 h), the effect of EGCG on MMP-2 expression, activity and its regulatory molecules were studied by gelatin zymography, Western blot, quantitative and semi-quantitative real time RT-PCR, immunoflourescence and cell adhesion assay. KEY FINDINGS: EGCG treatment reduced the activity, protein expression and mRNA expression level of MMP-2. EGCG treatment reduced the expression of focal adhesion kinase (FAK), membrane type-1-matrix metalloproteinase (MT1-MMP), nuclear factor-kappa B (NF-kB), vascular endothelial growth factor (VEGF) and reduced the adhesion of MCF-7 cells to ECM, fibronectin and vitronectin. Real time RT-PCR revealed a reduced expression of integrin receptors alpha5, beta1, alphav and beta3 due to EGCG treatment. SIGNIFICANCE: Down regulation of expression of MT1-MMP, NF-kB, VEGF and disruption of functional status of integrin receptors may indicate decreased MMP-2 activation; low levels of FAK expression might indicate disruption in FAK-induced MMP-2 secretion and decrease in activation of phosphatidyl-inositol-3-kinase (PI-3K), extracellular regulated kinase (ERK) indicates probable hindrance in MMP-2 regulation and induction. We propose EGCG as potential inhibitor of expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in MCF-7.
机译：目的：绿茶多酚表没食子儿茶素-3-没食子酸酯（EGCG）的抑癌作用已得到充分证明。研究表明，基质金属蛋白酶（MMP）通过基底膜和细胞外基质（ECM）的降解在肿瘤侵袭中起关键作用。我们研究了EGCG对基质金属蛋白酶-2（MMP-2）的影响，基质金属蛋白酶-2（MMP-2）是激活，分泌和信号转导分子的因子，可能与人类乳腺癌细胞MCF-7中MMP-2的调控有关。主要方法：用EGCG（20μM，24 h）处理MCF-7，通过明胶酶谱，Western blot，实时定量和半定量RT研究EGCG对MMP-2表达，活性及其调节分子的影响。 -PCR，免疫荧光和细胞粘附测定。主要发现：EGCG处理降低了MMP-2的活性，蛋白质表达和mRNA表达水平。 EGCG治疗可降低粘着斑激酶（FAK），膜1型基质金属蛋白酶（MT1-MMP），核因子-κB（NF-kB），血管内皮生长因子（VEGF）的表达并降低MCF的粘附-7细胞为ECM，纤连蛋白和玻连蛋白。实时RT-PCR显示由于EGCG处理，整联蛋白受体α5，β1，αv和β3的表达减少。意义：MT1-MMP，NF-kB，VEGF的表达下调和整联蛋白受体功能状态的破坏可能表明MMP-2的激活减少。 FAK表达水平低可能表明FAK诱导的MMP-2分泌受到破坏，磷脂酰肌醇3激酶（PI-3K）的激活降低，细胞外调节激酶（ERK）表明MMP-2调节和诱导可能受阻。我们提议通过涉及MCF-7中多个调控分子的过程，将EGCG作为pro-MMP-2的表达和活性的潜在抑制剂。

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