张佩,张春阳,张文文,等.体外重组IGFBP-6对 Akt,Erk,p38信号通路和血管生成的影响探究[J].中国海洋药物,2023,42(2):49-53.
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
投稿时间：2022-03-11  修订日期：2022-04-03
DOI：
中文关键词:  IGFBP-6  血管生成  信号通路
English Keywords:IGFBP-6  Angiogenesis  Signaling pathways
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作者单位E-mail
张佩 中国海洋大学 15850651061@163.com 
张春阳 中国海洋大学 chunyang.zhang559@gmail.com 
张文文 中国海洋大学 1181286078@qq.com 
李筠 中国海洋大学 yunlisun@ouc.edu.cn 
卢玲 中国海洋大学 linglu@ouc.edu.cn 
刘云章* 中国海洋大学医药学院 liuyz@ouc.edu.cn 
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中文摘要:
      目的 胰岛素样生长因子结合蛋白6(IGFBP-6)是潜在的抗癌新靶点,其能抑制肿瘤血管生成。本研究探讨重组IGFBP-6对Akt,Erk1/2以及p38信号通路的影响以及其是否通过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IGF配体结合结构域突变的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。本研究为寻找新的以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。
English Summary:
      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.
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