Duzgun Zekeriya, Korkmaz Funda Demirtaş, Akgün Egemen
Department of Medical Biology, Faculty of Medicine, Giresun University, Giresun, Turkey.
Mol Divers. 2025 Apr;29(2):1069-1078. doi: 10.1007/s11030-024-10891-z. Epub 2024 Jun 9.
Angiogenesis is the process by which new blood vessels are formed to meet the oxygen and nutrient needs of tissues. This process is vitally important in many physiological and pathological conditions such as tumor growth, metastasis, and chronic inflammation. Although the relationship of FDI-6 compound with FOXM1 protein is well known in the literature, its relationship with angiogenesis is not adequately elucidated. This study investigates the relationship of FDI-6 with angiogenesis and vascular endothelial growth factor B (VEGF-B) protein expression alterations. Furthermore, the study aims to elucidate the in silico interaction of FDI-6 with the VEGFR1 protein, a key player in initiating the angiogenic process, which is activated through its binding with VEGF-B. Our results demonstrate a significant effect of FDI-6 on cell viability. Specifically, we determined that the IC50 value of FDI-6 in HUVEC cells after 24 h of treatment is 24.2 μM, and in MDA-MB-231 cells after 24 h of application, it is 10.8 μM. These findings suggest that the cytotoxic effect of FDI-6 varies depending on the cell type. In wound healing experiments, FDI-6 significantly suppressed wound closure in MDA-MB-231 cells but did not show a similar effect in HUVEC cells. This finding suggests FDI-6 may have potential cell-type-specific effects. Molecular docking studies reveal that FDI-6 exhibits a stronger interaction with the VEGFR1 protein compared to its inhibitor, a novel interaction not previously reported in the literature. Molecular dynamic simulation results demonstrate a stable interaction between FDI-6 and VEGFR1. This interaction suggests that FDI-6 might modulate mechanisms associated with angiogenesis. Our Western blot analysis results show regulatory effects of FDI-6 on the expression of the VEGF-B protein. We encourage exploration of FDI-6 as a potential therapeutic agent in pathological processes related to angiogenesis. In conclusion, this study provides a detailed examination of the relationship between FDI-6 and both the molecular interactions and protein expressions of VEGF-B. Our findings support FDI-6 as a potential therapeutic agent in pathological processes associated with angiogenesis.
血管生成是形成新血管以满足组织对氧气和营养需求的过程。这一过程在许多生理和病理状况下至关重要，如肿瘤生长、转移和慢性炎症。尽管文献中已熟知FDI - 6化合物与FOXM1蛋白的关系，但其与血管生成的关系尚未得到充分阐明。本研究调查了FDI - 6与血管生成及血管内皮生长因子B（VEGF - B）蛋白表达改变的关系。此外，该研究旨在阐明FDI - 6与VEGFR1蛋白的计算机模拟相互作用，VEGFR1蛋白是启动血管生成过程的关键因子，通过与VEGF - B结合而被激活。我们的结果表明FDI - 6对细胞活力有显著影响。具体而言，我们确定处理24小时后FDI - 6在人脐静脉内皮细胞（HUVEC）中的IC50值为24.2μM，应用24小时后在MDA - MB - 231细胞中的IC50值为10.8μM。这些发现表明FDI - 6的细胞毒性作用因细胞类型而异。在伤口愈合实验中，FDI - 6显著抑制了MDA - MB - 231细胞的伤口闭合，但在HUVEC细胞中未显示出类似效果。这一发现表明FDI - 6可能具有潜在的细胞类型特异性作用。分子对接研究表明，与抑制剂相比，FDI - 6与VEGFR1蛋白表现出更强的相互作用，这是文献中此前未报道的新型相互作用。分子动力学模拟结果证明FDI - 6与VEGFR1之间存在稳定的相互作用。这种相互作用表明FDI - 6可能调节与血管生成相关的机制。我们的蛋白质印迹分析结果显示FDI - 6对VEGF - B蛋白的表达有调节作用。我们鼓励探索将FDI - 6作为血管生成相关病理过程中的潜在治疗药物。总之，本研究详细考察了FDI - 6与VEGF - B的分子相互作用及蛋白表达之间的关系。我们的研究结果支持FDI - 6作为血管生成相关病理过程中的潜在治疗药物。
