Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
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DOI：
10.1016/j.ejca.2007.07.010
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发表时间：
2007-09-01
影响因子：
8.4
通讯作者：
Graziani, Grazia
中科院分区：
文献类型：
--
作者：
Tentori, Lucio;Lacal, Pedro Miguel;Graziani, Grazia
聚（ADP-核糖）聚合酶（PARP）-1最近已被证明可促进肿瘤进展。由于血管生成是肿瘤生长的基本要求，我们研究了PARP抑制/缺失是否可能影响内皮细胞功能。为此，使用体内基质胶塞测定法研究了PARP抑制剂对PARP-1敲除小鼠中内皮细胞增殖、迁移、管形成和血管生成的影响。（对内皮PARP的IC 50：237 +/- 27 nM），浓度无细胞毒性作用（0.5-1 μ M），废除响应血管内皮生长因子或胎盘生长因子的迁移，阻碍管状网络的形成和体内血管生成受损。在PARP-1基因敲除小鼠中证实了PARP抑制剂的抗血管生成作用，这些结果为靶向PARP抗血管生成提供了证据，为PARP抑制剂在癌症治疗中的应用提供了新的治疗意义。(C)2007爱思唯尔有限公司版权所有。
Poly(ADP-ribose) polymerase (PARP)-1 has recently been shown to promote tumour progression. Since angiogenesis is an essential requirement for tumour growth, we examined whether PARP inhibition/deletion might affect endothelial cell functions. To this end, the influence of PARP inhibitors on endothelial cell proliferation, migration, tube formation and angiogenesis in PARP-1 knock-out mice, using an in vivo matrigel plug assay, was investigated.The results indicated that the PARP inhibitor GPI 15427 (IC50 on endothelial PARP: 237 +/- 27 nM), at concentrations devoid of cytotoxic effects (0.5-1 mu M), abrogated migration in response to vascular endothelial growth factor or placenta growth factor, hampered formation of tubule-like networks and impaired angiogenesis in vivo. The anti-angiogenic effect of the PARP inhibitor was confirmed in PARP-1 knock-out mice that displayed a defect of angiogenesis induced by growth factors.These results provide evidence for targeting PARP for anti- angiogenesis, adding novel therapeutic implications to the use of PARP inhibitors in cancer treatment. (C) 2007 Elsevier Ltd. All rights reserved.