Anti-angiogenic and vascular disrupting effects of C9, a new microtubule-depolymerizing agent.
作者： Xuan Ren , Mei Dai , Li-Ping Lin , Pui-Kai Li , Jian Ding
DOI: 10.1111/J.1476-5381.2009.00112.X
关键词:
摘要: Background and purpose: The critical role of blood supply in the growth solid tumours makes vessels an ideal target for anti-tumour drug discovery. anti-angiogenic vascular disrupting activities C9, a newly synthesized microtubule-depolymerizing agent, were investigated with several vitro vivo models. Possible mechanisms involved its activity also assessed. Experimental approach: Microtubule-depolymerizing actions assessed by surface plasmon resonance binding, competitive inhibition cytoskeleton immunofluorescence. Anti-angiogenic tested on proliferation, migration, tube formation human umbilical vein endothelial cells, rat aortic ring, chick chorioallantoic membrane Matrigel plug assays. Western blots Rho activation assays employed to examine Raf-MEK-ERK (mitogen-activated ERK kinase, extracellular signal-regulated kinase) Rho/Rho kinase signalling. Key results: C9 inhibited migration cells angiogenesis ring induced disassembly microtubules down-regulated signalling activated pro-angiogenic factors. In addition, disrupted capillary-like networks formed rapidly decreased perfusion neovasculature vivo. Endothelial cell contraction blebbing was dependent pathway. Conclusions implications: disruption associated changes morphology function involving pathways. These findings strongly suggest that is new microtubule-binding agent could effectively tumour vasculature.
sci-hub.se 参考文章(40)
Domenico Ribatti, Luisa Roncali, Angelo Vacca, Franco Dammacco, The chick embryo chorioallantoic membrane as a model for in vivo research on angiogenesis. The International Journal of Developmental Biology. ,vol. 40, pp. 1189- 1197 ,(1996) , 10.1387/IJDB.9032025
W Landuyt, O Verdoes, D.O Darius, M Drijkoningen, S Nuyts, J Theys, L Stockx, W Wynendaele, J.F Fowler, G Maleux, W Van den Bogaert, J Anné, A van Oosterom, P Lambin, Vascular targeting of solid tumours European Journal of Cancer. ,vol. 36, pp. 1833- 1843 ,(2000) , 10.1016/S0959-8049(00)00173-8
Barbara Imberti, Patrizia Borsotti, Raffaella Giavazzi, Giulia Taraboletti, Maura Poli, Michele Martinelli, Gianluca Micheletti, Vascular-targeting activity of ZD6126, a novel tubulin-binding agent. Cancer Research. ,vol. 63, pp. 1534- 1537 ,(2003)
Domenico Ribatti, Angelo Vacca, Luisa Roncali, Franco Dammacco, The Chick Embryo Chorioallantoic Membrane as a Model for in vivo Research on Anti-Angiogenesis Current Pharmaceutical Biotechnology. ,vol. 1, pp. 73- 82 ,(2000) , 10.2174/1389201003379040
Louis M. Sherwood, Edith E. Parris, Judah Folkman, Tumor Angiogenesis: Therapeutic Implications New England Journal of Medicine. ,vol. 285, pp. 1182- 1186 ,(1971) , 10.1056/NEJM197111182852108
Weihong Li, Yong Shao, Lihong Hu, Xiongwen Zhang, Yi Chen, Linjiang Tong, Chuan Li, Xu Shen, Jian Ding, BM6, a new semi-synthetic vinca alkaloid, exhibits its potent in vivo anti-tumor activities via its high binding affinity for tubulin and improved pharmacokinetic profiles. Cancer Biology & Therapy. ,vol. 6, pp. 787- 794 ,(2007) , 10.4161/CBT.6.5.4006
Wen-fu Tan, Xiong-wen Zhang, Mei-hong Li, Jian-min Yue, Yi Chen, Li-ping Lin, Jian Ding, Pseudolarix acid B inhibits angiogenesis by antagonizing the vascular endothelial growth factor-mediated anti-apoptotic effect European Journal of Pharmacology. ,vol. 499, pp. 219- 228 ,(2004) , 10.1016/J.EJPHAR.2004.07.063
Katherine L. Osusky, Dennis E. Hallahan, Allie Fu, Fei Ye, Yu Shyr, Ling Geng, The receptor tyrosine kinase inhibitor SU11248 impedes endothelial cell migration, tubule formation, and blood vessel formation in vivo, but has little effect on existing tumor vessels. Angiogenesis. ,vol. 7, pp. 225- 233 ,(2004) , 10.1007/S10456-004-3149-Y
Pui-Kai Li, Zili Xiao, Zhigen Hu, Bulbul Pandit, Yanjun Sun, Dan L Sackett, Karl Werbovetz, Andrew Lewis, Jayasekar Johnsamuel, None, Conformationally restricted analogs of Combretastatin A-4 derived from SU5416. Bioorganic & Medicinal Chemistry Letters. ,vol. 15, pp. 5382- 5385 ,(2005) , 10.1016/J.BMCL.2005.09.001
Annette Schmidt, Daniela Wenzel, Irmgard Thorey, Takako Sasaki, Jürgen Hescheler, Rupert Timpl, Klaus Addicks, Sabine Werner, Bernd K. Fleischmann, Wilhelm Bloch, Endostatin influences endothelial morphology via the activated ERK1/2-kinase endothelial morphology and signal transduction Microvascular Research. ,vol. 71, pp. 152- 162 ,(2006) , 10.1016/J.MVR.2006.01.001