期刊
EUROPEAN JOURNAL OF CANCER
卷 43, 期 14, 页码 2124-2133出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2007.07.010
关键词
poly(ADP-ribose) polymerase; angiogenesis; endothelial cells; PARP inhibitors; anti-angiogenic compounds
类别
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.
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