姜黄素抑制HGF诱导血管内皮细胞迁移和VEGF表达的体内外研究

目的:探索姜黄素抑制肝细胞生长因子(HGF)诱导血管生成的分子机制。方法:利用管腔形成实验、划痕实验、Western blot实验和动物实验观察姜黄素、c-Met抑制剂SU11274、磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002和m TOR抑制剂rapamycin对HGF诱导的内皮细胞迁移、管腔形成能力、血管内皮生长因子(VEGF)表达、相关信号通路和瘤体内血管密度的影响。结果:姜黄素可显著抑制HGF诱导内皮细胞发生迁移、小管形成及VEGF的表达,同时抑制c-Met/AKT/m TOR/S6通路的磷酸化,并可减少瘤体内VEGF的表达和微血管密度。使用c-Met抑制剂SU11274、PI3K抑制剂LY294002或m TOR抑制剂rapamycin能得到和姜黄素相似的效应。结论:姜黄素抑制HGF诱导的血管生成可能是通过抑制c-Met/AKT/m TOR/S6信号通路活化实现的。

Curcumin inhibits HGF induced vascular endothelial cell migration and VEGF expression in vitro and in vivo

ATM: To explore the molecular mechanism that curcumin inhibits hepatocyte growth factor (HGF) induced angiogenesis. METHODS: The effects of curcumin, c-Met inhibitor SU11274, phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and mTOR inhibitor rapamycin on HGF-induced endothelial cell migration, tubule formation ability, vascular endothelial growth factor (VEGF) expression, related signaling pathways and the density of blood vessels in tumors were observed by the methods of capillary forming experiments, wound healing assay, Western blot and animal study. RESULTS: SU11274, LY294002, rapamycin and curcumin significantly inhibited HGF induced endothelial cell migration, tubule formation and VEGF expression, suppressed the phosphorylation of c-Met/AKT/mTOR/S6 pathway related molecules, reduced VEGF expression and microvascular density in the tumors. CONCLUSION: Curcumin inhibits HGF induced angiogenesis by inhibiting c-Met/AKT/mTOR/S6 pathway activation.