Nimbolide retards tumor cell migration, invasion, and angiogenesis by downregulating MMP‐2/9 expression via inhibiting ERK1/2 and reducing DNA‐binding activity of NF‐κB in colon cancer cells
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Nimbolide, a plant-derived limonoid has been shown to exert its antiproliferative effects in various cell lines. We demonstrate that nimbolide effectively inhibited proliferation of WiDr colon cancer cells through inhibition of cyclin A leading to S phase arrest. It also caused activation of caspase-mediated apoptosis through the inhibition of ERK1/2 and activation of p38 and JNK1/2. Further nimbolide effectively retarded tumor cell migration and invasion through inhibition of metalloproteinase-2/9 (MMP-2/9) expression, both at the mRNA and protein level. It was also a strong inhibitor of VEGF expression, promoter activity, and in vitro angiogenesis. Finally, nimbolide suppressed the nuclear translocation of p65/p50 and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression.Matrix (chemical analysis)
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Angiogenesis inhibitor
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Angiogenesis, a formation of neovessels, is regulated by the local balance between angiogenesis stimulators and inhibitors. A number of such endogenous regulators of angiogenesis have been found in the body. Recently, vasohibin-1 (VASH1) was isolated as a negative feedback regulator of angiogenesis produced by endothelial cells (ECs) and subsequently vasohibin-2 (VASH2) as a homologue of VASH1. It was then explored that VASH1 is expressed in ECs to terminate angiogenesis, whereas VASH2 is expressed in cells other than ECs to promote angiogenesis in the mouse model of angiogenesis. This review will focus on the vasohibin family members, which are novel regulators of angiogenesis.
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Angiogenesis is regulated by a local balance between the levels of endogenous stimulators and inhibitors of angiogenesis. Understanding of the mechanism of angiogenesis has advanced significantly since the discovery of two members of the family of angiogenesis stimulators, i.e., vascular endothelial growth factor family proteins and angiopoietins. These factors act on endothelial cells to stimulate angiogenesis. In contrast, most of angiogenesis inhibitors do not seem to have such characteristics. Very few genes encoding molecules that selectively inhibit angiogenesis have been discovered. This review will focus on our current understanding of endogenous inhibitors of angiogenesis.
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Chorioallantoic membrane
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Angiogenesis 为许多生理、病理学的过程是很重要的。然而， angiogenesis 的分子的机制是不清楚的。阐明 angiogenesis 并且到的分子的机制为 angiogenesis 依赖的疾病开发处理，建立是必要的一在 vitro angiogenesis 合适模型。在这研究，我们基于一台 microfluidic 设备在 vitro angiogenesis 模型创造了一篇小说。我们的模型提供一在里面为 endothelial 房间(EC ) 的象 vivo 一样微型环境文化和监视器到在他们在实时的微型环境的变化的 EC 的反应。为了为研究 angiogenesis， EC 增长上的 pro-angiogenic 因素的效果，迁居和像试管的结构形成评估这台 microfluidic 设备的潜力，被调查。我们的结果证明在 3D 矩阵的 EC 的增长率被 pro-angiogenic 因素显著地支持(随 59.12% 的增加) 。与 pro-angiogenic 因素坡度的刺激，方向性地从低集中移植进 Matrigel 到高集中并且因而的 EC 形成了多房间弦和像试管的结构。这些结果建议设备能为阐明提供一个合适的平台 angiogenesis 并且为为 angiogenesis 依赖的疾病屏蔽 pro-angiogenic 或 anti-angiogenic 药的机制。
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Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic enzymes able to cleave all major protein components in the extracellular matrix during the processes of wound healing and tumor formation. Tissue inhibitors of MMPs (TIMPs) , which exist in the human body, can regulate the activity of MMPs. According to different sources, MMP inhibitors are divided into TIMPs, natural MMP inhibitors and synthetic inhibitors. The classification and functional features of MMPs and MMP inhibitors are summarized and the relationship between MMPs, MMP inhibitors and posterior capsular opacification (PCO) are reviewed.
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Matrix metalloproteinases; Matrix metalloproteinase inhibitors; Cataract, secondary
Matrix metalloproteinase inhibitor
Proteolytic enzymes
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