TNP-470 and recombinant human interferon-α2a inhibit angiogenesis synergistically
TNP-470 and recombinant human interferon-α2a inhibit angiogenesis synergistically
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DOI：
10.1046/j.1365-2141.2000.02087.x
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发表时间：
2000-06-01
影响因子：
6.5
通讯作者：
Dammacco, F
中科院分区：
文献类型：
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作者：
Minischetti, M;Vacca, A;Dammacco, F
两种已知的抗血管生成剂TNP-470和干扰素（IFN）-α的组合发挥协同作用的假设已经在体外和体内进行了研究。在体外，TNP-470和重组人IFN-α 2a（rhIFN-α 2a）导致人脐静脉内皮细胞（HUVEC）和EA.hy926内皮细胞增殖的剂量依赖性抑制。与单独使用的两种药物在其最低或无效剂量相比，相同剂量的联合治疗在没有细胞毒性的情况下抑制更强烈，并且在Matrigel上显示出对细胞趋化性和毛细血管形态发生的类似行为。然而，基质金属蛋白酶2（MMP-2）和MMP-9的分泌不受这两种药物的影响，无论是单独或组合，即使当他们在其最低有效剂量或在较高的细胞毒性剂量。鸡胚绒毛尿囊膜（CAM）-海绵测定的体内实验显示了相同的剂量依赖性抑制和协同作用。由于CAM-海绵模型中碱性成纤维细胞生长因子（bFGF）诱导的血管生成被联合治疗强烈抑制，TNP-470和rhIFN-α 2a似乎协同发挥抗血管生成作用，可能是通过干扰bFGF介导的途径。
The hypothesis that the combination of two known antiangiogenic agents TNP-470 and interferon (IFN)-alpha exerts synergistic effects has been investigated in vitro and in vivo. In vitro, TNP-470 and recombinant human IFN-alpha 2a (rhIFN-alpha 2a) resulted in a dose-dependent inhibition of proliferation of human umbilical vein endothelial cells (HUVECs) and EA.hy926 endothelial cells. Compared with the two agents used singly at their lowest or ineffective doses, combined treatment with the same doses inhibited more intensely in the absence of cytotoxicity and displayed similar behaviour on cell chemotaxis and capillary morphogenesis on Matrigel. However, the secretion of matrix metalloproteinase 2 (MMP-2) and MMP-9 was not influenced by the two agents, either alone or in combination, even when they were applied at their lowest efficacious doses or at higher cytotoxic doses. Experiments in vivo with the chick embryo chorioallantoic membrane (CAM)-sponge assay revealed the same dose-dependent inhibition and synergy. As the basic fibroblast growth factor (bFGF)-induced angiogenesis in the CAM-sponge model was strongly inhibited by the combined treatment, TNP-470 and rhIFN-alpha 2a would appear to exert antiangiogenesis synergistically, perhaps by interfering with the bFGF-mediated pathway.