丁香酸通过下调斑马鱼胚胎中VEGF发挥抗血管生成活性

Gowri Karthik , Mangalagowri Angappan , Arunkumar VijayaKumar , Sukumaran Natarajapillai
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引用次数: 21

摘要

血管生成,即新血管的形成,对维持正常细胞功能至关重要。血管生成的功能障碍和/或增加可能导致不受控制的细胞增殖,从而导致癌症。利用天然化合物抑制血管生成因子在癌症研究中有很大的希望。因此,我们利用斑马鱼胚胎体内模型研究了丁香酸(SA)这种天然存在的酚酸的抗血管生成特性。对SA处理后的胚胎进行形态学观察,以评价该化合物的毒性。采用红细胞染色法评价ISV对斑马鱼胚胎的抑制作用。此外,为了确定ISV抑制的机制,采用实时逆转录酶聚合酶链反应和western blot分析分别评估VEGF mRNA和蛋白的表达。结果表明,在50μM范围内,SA对形貌没有影响。在20 ~ 50 μM范围内有明显的血管生成作用,与对照组相比,显著减少了ISV区循环红细胞的数量。在50 μM时,胚胎ISV区未见红细胞。Real-time PCR和western blot分析显示,SA对VEGF mRNA和VEGF蛋白的表达均呈剂量依赖性。综上所述,丁香酸可能通过下调VEGF介导的通路而具有抗血管生成活性,从而具有潜在的治疗效果,有望成为抗癌的武器。
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Syringic acid exerts antiangiogenic activity by downregulation of VEGF in zebrafish embryos

Angiogenesis, the formation of new blood vessels is essential for the conservancy of normal cell functions. The dysfunction and/or increase in angiogenesis may lead to uncontrolled cell proliferation of cells resulting in cancer. Inhibiting angiogenic factors using natural compound has substantial hope in cancer research. Hence, we investigated syringic acid (SA), a naturally occurring phenolic acid for its antiangiogenic property using the zebrafish embryo in vivo model. Morphological observations of the SA treated embryos were analyzed to evaluate the toxicity of the compound. RBC staining was performed to evaluate the ISV inhibition in zebrafish embryos. Further, to determine the mechanism behind ISV inhibition, a real-time reverse-transcriptase polymerase chain reaction and western blot analysis was done to evaluate VEGF mRNA and protein expression respectively. Our result showed that SA didn’t affect the morphology up to 50μM. The apparent angiogenic effect was seen from 20 to 50 μM, which significantly reduced number of circulating red blood cells in ISV region compared to that of control. At 50 μM there was no visible RBC present in the ISV region of the embryos. Further, Real-time PCR and western blot analysis showed, SA inhibited VEGF mRNA expression and protein expression respectively in a dose dependent manner. These findings altogether suggest that syringic acid may have antiangiogenic activity by down regulating VEGF mediated pathway thereby having potential therapeutic benefit and promises to be a weapon against cancer.

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