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目的:研究微管抑制剂C9对新生血管生成的抑制作用及其机制。方法:利用流式细胞术和TUNEL法,检测C9逆转血管内皮生长因子(vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)抗无血清诱导的内皮细胞凋亡;Western Blot法检测C9对生长因子VEGF和bFGF刺激的下游与新生血管生成相关的两条通路Raf-Mek-Erk和PI3K-AKT中Raf,Mek,Erk,Akt磷酸化影响。结果:C9能够逆转VEGF和bFGF抗无血清诱导的内皮细胞凋亡,可以剂量依赖性地下调生长因子VEGF和bFGF下游与新生血管生成相关的两条通路Raf-Mek-Erk和PI3K-AKT中Raf,Mek,Erk,Akt磷酸化,但是对VEGF受体KDR及bFGF受体FGFR1的磷酸化没有影响。结论:C9主要通过直接抑制Raf-Mek-Erk信号通路而抑制生长因子的抗内皮细胞凋亡作用,并产生抑制新生血管生成作用。
Objective: To investigate the inhibitory effect of microtubule inhibitor C9 on neovascularization and its mechanism. Methods: Flow cytometry and TUNEL were used to detect C9 reversal of serum-induced endothelial cell apoptosis (VEGF) and basic fibroblast growth factor (bFGF) The effects of C9 on the phosphorylation of Raf, Mek, Erk and Akt in Raf-Mek-Erk and PI3K-AKT cells were detected by Western Blot. Results: C9 could reverse the anti-serum-induced endothelial cell apoptosis induced by VEGF and bFGF and down-regulate the two pathways Raf-Mek-Erk and PI3K-AKT in the downstream of VEGF and bFGF in a dose-dependent manner , Mek, Erk, Akt phosphorylation, but had no effect on VEGF receptor KDR and phosphorylation of bFGF receptor FGFR1. CONCLUSION: C9 inhibits the anti-endothelial cell apoptosis of growth factor mainly through the direct inhibition of Raf-Mek-Erk signal pathway, and inhibits the angiogenesis of neovascularization.