Kallistatin, a novel anti-angiogenesis agent, inhibits angiogenesis via inhibition of the NF-κB signaling pathway
| Autor: | Y. Diao, H.Y. Yang, G.Q. Xiao, X.P. Huang, Junsheng Lin, K.F. Huang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis Angiogenesis Inhibitors Breast Neoplasms Chick Embryo IκB kinase Biology Chorioallantoic Membrane Rats Sprague-Dawley chemistry.chemical_compound Human Umbilical Vein Endothelial Cells Animals Humans Neoplasm Metastasis Serpins Pharmacology Dose-Response Relationship Drug Neovascularization Pathologic NF-kappa B NF-κB General Medicine Rats Angiogenesis inhibitor Gene Expression Regulation Neoplastic Vascular endothelial growth factor IκBα chemistry Kallistatin Immunology MCF-7 Cells Cancer research Female Signal transduction Signal Transduction |
| Zdroj: | Biomedicine & Pharmacotherapy. 68:455-461 |
| ISSN: | 0753-3322 |
| DOI: | 10.1016/j.biopha.2014.03.005 |
| Popis: | Development of a novel angiogenesis inhibitor will be essential for the improvement of therapeutics against cancer. Kallistatin had been recognized as an endogenous angiogenesis inhibitor. Here, we demonstrated kallistatin's strong anti-angiogenesis and anti-metastasis activity stimulated by breast cancer cells (MCF-7) and its mechanism of action in vitro. The anti-angiogenesis effect in vivo was evaluated by chicken chorioallantoic membrane (CAM) neovascularisation. Because of the underlying molecular mechanism of its anti-angiogenesis activity remains poorly understood. In this study, we examined whether the NF-κB signaling pathway was involved in the anti-angiogenesis and anti-metastasis activity of kallistatin. Kallistatin significantly inhibited TNF-α-induced nuclear factor-κB activation in a dose-dependent manner. Addition of kallistatin inhibited TNF-α induced IκBα degradation; phosphorylation of IκBα kinase (IKK), nuclear factor-κB-p65 protein; and nuclear translocation of p65/50. Meanwhile, we investigated the effects of kallistatin on the expression of vascular endothelial growth factor (VEGF) and other angiogenesis-related gene in human umbilical vein endothelial cells (HUVECs). We found that kallistatin decreased the expression of VEGF and some angiogenesis-related genes, which promoted angiogenesis in cancer. Taken together, we suggested that kallistatin would inhibit tumor angiogenesis via inhibition of the NF-κB signaling pathway and finally abrogate NF-κB-dependent gene expression. All the results revealed that kallistatin would have potential as a novel. |
| Databáze: | OpenAIRE |
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