Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis
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- 作者：Lucio Tentori ; Pedro Miguel Lacal ; Alessia Muzi ; Annalisa Susanna Dorio ; Carlo Leonetti ; Marco Scarsella ; Federica Ruffini ; Weizheng Xu ; Wokee Min ; Antonella Stoppacciaro ; Cristina Colarossi ; Zhao-Qi
- 关键词：Poly(ADP-ribose) polymerase ; Angiogenesis ; Endothelial cells ; PARP inhibitors ; Anti-angiogenic compounds
- 刊名：European Journal of Cancer
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：43
- 期：14
- 页码：2124-2133
- 全文大小：690 K
文摘
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 μM), 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.