Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2
Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2
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DOI：
10.1186/2045-824x-3-12
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Chevanne, Marta
中科院分区：
文献类型：
--
作者：
Caldini, Riccardo;Fanti, Elena;Chevanne, Marta
背景资料：聚腺苷二磷酸核糖聚合酶（Poly（ADP-Ribose）polymerase，PARP）活性在DNA修复、细胞增殖和分化等细胞过程中起着重要作用。特别地，最近发现PARP活性影响人脐静脉内皮细胞的增殖、迁移和管形成。近年来，PARP抑制剂已进入临床试验，通过阻止DNA修复来加强癌症治疗，但对不同药物浓度对肿瘤生长的重要步骤--新血管生成的影响知之甚少。方法：用PARP抑制剂3氨基苯甲酰胺（3ABA）处理人脐静脉内皮细胞，并测试几种不同的细胞参数。在这里，我们目前在体外的证据表明，低浓度的3ABA（50 μ M），刺激血管生成，通过降低纤溶活性，进行尿激酶型纤溶酶原激活剂（uPA），并通过增强基质金属蛋白酶-2（MMP-2）明胶溶解活性，在成纤维细胞生长因子-2刺激的内皮细胞。这些不平衡的途径修改在体外血管生成的步骤，抑制chemoinvasion和刺激tubulogenic activity.Conclusions：我们的研究结果表明，促血管生成的影响低浓度的3ABA警报PARP抑制剂的疗效，以加强抗癌治疗。此外，他们指出，内皮细胞的化学侵袭和微管依赖于不同的蛋白水解途径。
Background: Poly(ADP-Ribose) polymerase (PARP) activity has been demonstrated fundamental in many cellular processes, including DNA repair, cell proliferation and differentiation. In particular, PARP activity has been recently found to affect proliferation, migration, and tube formation of human umbilical vein endothelial cells. In recent times, PARP inhibitors have entered in clinical trials topotentiate cancer treatments by preventing DNA repair, but little is known about the effects performed by different drug concentrations on neoangiogenesis, an essential step in tumor growth.Methods: Human umbilical vein endothelial cells were treated with 3 aminobenzamide (3ABA), a PARP inhibitor, and tested for several different cellular parameters.Results: Here we present in vitro evidence that a low concentration of 3ABA (50 mu M), stimulates angiogenesis by decreasing fibrinolytic activity, carried out by urokinase-type plasminogen activator (uPA), and by enhancing matrix metalloprotease-2 (MMP-2) gelatinolytic activity, in fibroblast growth factor-2-stimulated endothelial cells. These unbalanced pathways modify in vitro angiogenic steps, inhibiting chemoinvasion and stimulating tubulogenic activity.Conclusions: Our results suggest that the proangiogenic effect of low concentrations of 3ABA alerts on the efficacy of PARP inhibitors to potentiate anticancer therapy. Moreover, they indicate that endothelial chemoinvasion and tubulogenesis depend on distinct proteolytic pathways.