Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells
Resveratrol induces MMP-9 and cell migration via the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells
复制标题
DOI：
10.3892/or.2012.2151
复制
发表时间：
2013-02-01
期刊：
影响因子：
4.2
通讯作者：
Kim, Song Ja
中科院分区：
文献类型：
--
作者：
Gweon, Eun Jeong;Kim, Song Ja
Trans-3,4',5-三羟基芪（白藜芦醇）是一种葡萄多酚，存在于各种植物、食品、红酒和葡萄中。白藜芦醇具有抗炎、抗癌、抗氧化和抗衰老特性。基质金属蛋白酶（MMP）是参与细胞外基质降解的关键酶，其表达可能在癌症转移中受到调节。在本研究中，我们旨在评估白藜芦醇对基质金属蛋白酶和细胞迁移的影响，并了解其在 HT1080 人纤维肉瘤细胞中的作用机制。通过 MTT 测定和 FACS 分析检测，我们发现白藜芦醇在不同浓度下抑制 HT1080 细胞活力。然而，根据明胶酶谱分析和蛋白质印迹分析确定，白藜芦醇以剂量和时间依赖性方式显着增加 MMP-9 的活化和表达。我们还发现，根据伤口愈合试验的结果，白藜芦醇增强了 HT1080 细胞的迁移能力，并降低了 p38 激酶的磷酸化。此外，HT1080 细胞中的 Akt 激酶被白藜芦醇抑制。 SB203580 和 LY294002 对 p38 和 Akt 激酶的抑制进一步增加了白藜芦醇诱导的 MMP-9 以及 HT1080 细胞中的细胞迁移。我们的结果表明，白藜芦醇通过 HT1080 人纤维肉瘤细胞中的 p38 激酶和 PI-3K 途径调节 MMP-9 和迁移能力。
Trans-3,4',5-trihydroxystilbene (resveratrol) is a grape polyphenol present in various plants, food products, red wine and grapes. Resveratrol has anti-inflammatory, anti-carcinogenic, anti-oxidant and anti-aging properties. Matrix metalloproteinases (MMPs) are key enzymes involved in the degradation of the extracellular matrix, and their expression may be regulated in cancer metastasis. In the present study, we aimed to evaluate the effect of resveratrol on MMPs and cell migration, and to understand the mechanism of action in HT1080 human fibrosarcoma cells. We found that resveratrol inhibited HT1080 cell viability at various concentrations as detected by the MTT assay and FACS analysis. However, resveratrol dramatically increased the activation and expression of MMP-9 in a dose- and time-dependent manner, as determined by gelatin zymography assay and western blot analysis. We also discovered that resveratrol enhanced the migratory ability of HT1080 cells, as determined by the wound healing assay, and decreased the phosphorylation of p38 kinase. Moreover, the Akt kinase was inhibited by resveratrol in the HT1080 cells. The inhibition of p38 and Akt kinases with SB203580 and LY294002 further increased resveratrol-induced MMP-9 as well as cell migration in the HT1080 cells. Our results suggest that resveratrol regulates MMP-9 and migratory abilities through the p38 kinase and PI-3K pathways in HT1080 human fibrosarcoma cells.