Anti-angiogenesis effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model
Anti-angiogenesis effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model
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DOI：
10.1111/1440-1681.12907
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发表时间：
2018-04-01
影响因子：
2.9
通讯作者：
Mirshafiey, Abbas
中科院分区：
文献类型：
--
作者：
Rastegari-Pouyani, Mohsen;Mostafaie, Ali;Mirshafiey, Abbas
血管生成是一个过程，通过该过程，新的毛细血管从预先存在的毛细血管形成，这显著有助于许多疾病的发病机制，如癌症和慢性炎症性疾病。- D-甘露糖醛酸（M2000）是一种新型的非甾体抗炎药（NSAID），具有免疫抑制作用，是一种基质金属蛋白酶（MMP）抑制剂。本研究旨在研究M2000在体内外模型下的抗血管生成作用。台盼蓝法检测M2000的细胞毒作用，MTT法检测M2000的抗增殖作用。然后使用3D胶原蛋白-cytodex模型和鸡绒膜尿囊膜（CAM）试验来评价M2000的抗血管生成性能。细胞毒性试验显示，M2000（浓度低于100 μ g/mL）对人脐静脉内皮细胞（HUVEC）无细胞毒性作用。还说明M2000对HUVECs几乎没有或没有抗增殖作用。此外，M2000的抗血管生成作用在体外模型中显示为边缘性的，在体内状态中显示为显著的且具有剂量依赖性。这项研究表明，M2000可以被认为是一种抗血管生成分子，更可能主要通过对内皮细胞的间接作用发挥其活性，其抗炎作用可能部分归因于其抗血管生成活性。因此，它可以被推荐作为预防和治疗癌症，慢性炎症性疾病和其他血管生成相关疾病的候选药物。
Angiogenesis is a process through which new capillaries are formed from pre-existing ones, which contributes significantly to the pathogenesis of numerous diseases, such as cancer and chronic inflammatory disorders. The -D-mannuronic acid (M2000) is a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive effects and is a matrix metalloproteinase (MMP) inhibitor. This research aimed to study the anti-angiogenesis effects of M2000 under in vitro and in vivo models. The cytotoxic and anti-proliferative effects of M2000 were examined using the trypan blue method and the MTT assay, respectively. The 3D collagen-cytodex model and the chickchorioallantoic membrane(CAM) assay were then used to evaluate the anti-angiogenesis property of M2000. Cytotoxicity assay revealed that M2000 (at concentrations of less than 100 mu g/mL) had no cytotoxic effect on human umbilical vein endothelial cells(HUVECs). It was also illustrated that M2000 had little or no anti-proliferative effect on HUVECs. In addition, the anti-angiogenesis effects of M2000 were shown to be marginal in the in vitro model and both significant and dose-dependent in the in vivo status. This study showed that M2000 could be considered as an anti-angiogenic molecule which more likely exerts its activity mainly via indirect effects on endothelial cells and its anti-inflammatory effects may partly be attributable to its anti-angiogenic activity. Therefore, it could be recommended as a candidate for prevention and treatment of cancer, chronic inflammatory diseases, and other angiogenesis-related disorders.