体外重组IGFBP-6对Akt、Erk、p38信号通路和血管生成的影响探究  

Effects of IGFBP-6 on Akt,Erk,p38 signaling pathways and angiogenesis in vitro

作　　者：张佩 张春阳 张文文 李筠[1] 卢玲[1] 刘云章[1] ZHANG Pei;ZHANG Chun-yang;ZHANG Wen-wen;LI Yun;LU Ling;LIU Yun-zhang(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛266003

出　　处：《中国海洋药物》2023年第2期49-53,共5页Chinese Journal of Marine Drugs

基　　金：国家自然科学基金项目(31772457)资助。

摘　　要：目的探讨重组胰岛素样生长因子结合蛋白6(IGFBP-6)对Akt、Erk1/2以及p38信号通路的影响,研究其是否通过Akt、Erk1/2以及p38信号通路对血管生成发挥作用。方法通过不同浓度的IGFBP-6重组蛋白处理HUVEC细胞检测Akt、Erk1/2以及p38信号通路是否激活。运用不同浓度胰岛素样生长因子(insulin-like growth factor,IGF)结合结构域突变的mIGFBP-6体外重组蛋白处理HUVEC细胞,检测Akt、Erk1/2以及p38信号通路的激活是否依赖IGF配体。采用这3条通路特异性的抑制剂进行体外血管生成实验,进一步探究IGFBP-6抑制血管生成与Akt、Erk1/2以及p38信号通路的关系。结果IGFBP-6能够激活HUVEC细胞的Akt、Erk1/2以及p38信号通路,且这种激活作用具有IGF配体非依赖性。Akt、Erk1/2以及p38信号通路的抑制剂不能营救IGFBP-6对血管形成的抑制作用。结论IGFBP-6抑制血管生成的作用不依赖Akt、Erk1/2以及p38信号通路。为寻找新的以IGFBP-6为靶点的抗血管生成候选化合物,包括海洋来源的抗血管生成的小分子筛选提供了一定的理论依据。Objective Insulin-like growth factor binding protein 6(IGFBP-6)is a potential new anti-tumor target that inhibits tumor angiogenesis.This study investigated the effects of recombinant IGFBP-6 on Akt,Erk1/2 and p38 signaling pathways and whether IGFBP-6 plays a role in angiogenesis through Akt,Erk1/2 and p38 signaling pathways.Methods HUVEC cells were treated with different concentrations of recombinant protein IGFBP-6 to detect the activation of Akt,Erk1/2 and p38 signaling pathways.HUVEC cells were treated mIGFBP-6 with IGF binding domain mutated in vitro to detect whether activation of Akt,Erk1/2 and p38 signaling pathways depends on IGF.Specific inhibitors for these three pathways were used to conduct in vitro angiogenesis assay to explore the relationship between inhibition of angiogenesis by IGFBP-6 and Akt,Erk1/2,p38 signaling pathways.Results IGFBP-6 can activate Akt,Erk1/2 and p38 signaling pathways in HUVEC cells,and it is IGF independent.Inhibitors of Akt,Erk1/2 and p38 signaling pathways cannot rescue IGFBP-6 from its inhibition of angiogenesis.Conclusion IGFBP-6 inhibits angiogenesis independent of Akt,Erk1/2 and p38 signaling pathways.This study provides a theoretical basis for the search for novel anti-angiogenesis candidate compounds targeting IGFBP-6,including small molecules of Marine origin.

关 键 词：IGFBP-6 血管生成 信号通路 

分 类 号：R965[医药卫生—药理学]