Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect
Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect
复制标题
DOI：
10.1016/j.lfs.2009.09.003
复制
发表时间：
2009-10-21
期刊：
影响因子：
6.1
通讯作者：
Liao, Hui-Fen
中科院分区：
文献类型：
--
作者：
Chen, Yu-Jen;Tsai, Yin-Meng;Liao, Hui-Fen
目的：本研究探讨了合成的小分子抗肿瘤化合物去甲斑蝥素（normandaridin，NCTD）在体外和体内的促血管生成作用。主要方法：将同基因结肠癌CT 26细胞移植到小鼠体内，观察NCTD对VEGF生成的影响及肝肾毒性。使用人脐静脉内皮细胞（HUVECs）来检查NCTD对活力、趋化性、血管网管形成、粘附能力、失巢凋亡和丝裂原活化蛋白激酶（MAPK）信号传导的体外作用。一个蛋白质阵列被用来分析血管生成因子释放NCTD处理HUVECs.Key发现：NCTD抑制荷瘤小鼠的血浆VEGF水平，没有肾或肝毒性。在体外，NCTD抑制正常HUVECs的活力的程度低于CT 26癌细胞。在浓度低于抑制50%细胞的浓度时，NCTD抑制HUVECs的迁移和毛细血管样管的形成。NCTD的抗血管生成作用伴随着失巢凋亡、整合素β 1的下调和波形蛋白的分解。NCTD降低磷酸化（p）-JNK和p-ERK的MAPK表达。P-P38表达或P38抑制剂SB 203580不损害NCTD对HUVECs活力或粘附的影响。此外，NCTD抑制促血管生成因子从HUVECs的释放，但不从CT 26 cells.Significance：NCTD是一种合成的，具有抗血管生成活性的小分子化合物，作为抗转移和抗血管生成剂在抗癌治疗中具有潜在的用途。(C)2009 Elsevier Inc. All rights reserved.
Aims: This study examined the in vitro and in vivo angiogenic effects of norcantharidin (NCTD), a synthetic, small-molecule antitumor compound.Main methods: Syngeneic colorectal adenocarcinoma CT26 cells were implanted in mice to examine the effect of NCTD on VEGF production and renal and hepatic toxicity. Human umbilical endothelial cells (HUVECs) were used to examine the in vitro effect of NCTD on viability, chemotaxis, vascular network tube formation, adhesive ability, anoikis, and mitogen-activated protein kinase (MAPK) signaling. A protein array was used for analysis of angiogenic factors released from NCTD-treated HUVECs.Key findings: NCTD suppressed plasma VEGF levels of tumor-bearing mice, without renal or hepatic toxicity. In vitro, NCTD inhibited viability of normal HUVECs to a lesser extent than CT26 cancer cells. At concentrations less than those inhibiting 50% of the cells, NCTD inhibited migration and capillary-like tube formation of HUVECs. The anti-angiogenic effect of NCTD was accompanied by anoikis, down-regulation of integrin beta 1, and breakdown of vimentin. NCTD decreased MAPK expression of phosphorylated (p)-JNK and p-ERK. P-P38 expression or P38 inhibitor SB203580 did not impair the effect of NCTD on viability or adhesion of HUVECs. In addition, NCTD inhibited the release of pro-angiogenic factors from HUVECs, but not from CT26 cells.Significance: NCTD is a synthetic, small-molecule compound possessing anti-angiogenetic activity with potential use in anti-cancer therapy as an anti-metastatic and anti-angiogenic agent. (C) 2009 Elsevier Inc. All rights reserved.