Angiogenesis is a new vessel formation process that plays a role in various physiological and pathological conditions. This process is controlled by the balance between pro-angiogenic and anti-angiogenic mediators in the organism. Angiogenesis is needed for the growth and metastasis of solid tumors. Therefore, the anti-angiogenic treatment approach is seen as an interesting option in cancers. Fenretinide, a synthetic retinoic acid analog, is an effective agent on angiogenesis. In this study, we aimed to investigate the effects of the fenretinide on some miRNAs involving in angiogenesis process and on the expression of CDH5, FOXM1 and eNOS genes upregulated in angiogenesis. In addition, it was shown the effects of this agent on cell proliferation, cell migration and capillary-like tube formation. In our study, the data were analyzed using Kruskal-Wallis and Dunn's test. Fenretinide applied to the cells for 24 and 48 h periods reduced cell proliferation (P < 0.001) and cell migration, and suppressed tube formation (P < 0.001) as a dose dependent manner. Endothelial cells were cultured in growth-inducing media containing a variety of growth factors such as VEGF, FGF, IGF and EGF. As a result of simultaneous PCR analysis, we found that angiogenesis-promoting miR-10b was effectively suppressed (P < 0.001) and interestingly angiogenesis-modulating miR-126 was slightly increased (P < 0.05), but other miRNAs, including miR-31, miR-21, miR-101, miR-340, miR-29c, miR-206 and miR-146a were not affected. Besides, a significant decrease was observed in the levels of some angiogenesis-inducing genes, CDH5 (P < 0.001), FOXM1 (P < 0.001) and eNOS (P < 0.01 and P < 0.001) in endothelial cells treated with fenretinide. Our results have shown that fenretinide exhibited anti-angiogenic activity through the down-regulation of CDH5, FOXM1 and eNOS genes, and suppression of miR-10b.

中文翻译：

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Fenretinide通过下调CDH5，FOXM1和eNOS基因并抑制microRNA-10b来减少血管生成。

血管生成是在各种生理和病理状况中起作用的新的血管形成过程。该过程由生物体内促血管生成和抗血管生成介质之间的平衡控制。实体瘤的生长和转移需要血管生成。因此，抗血管生成治疗方法被认为是癌症中一种有趣的选择。芬维A胺，一种合成的维甲酸类似物，是血管生成的有效药物。在这项研究中，我们旨在研究芬维A胺对一些参与血管生成过程的miRNA以及血管生成中上调的CDH5，FOXM1和eNOS基因表达的影响。另外，显示了该试剂对细胞增殖，细胞迁移和毛细管样管形成的作用。在我们的研究中 使用Kruskal-Wallis和Dunn检验分析数据。Fenretinide应用于细胞24和48小时，以剂量依赖性方式减少细胞增殖（P <0.001）和细胞迁移，并抑制管形成（P <0.001）。内皮细胞在含有多种生长因子如VEGF，FGF，IGF和EGF的生长诱导培养基中培养。作为同时进行PCR分析的结果，我们发现促进血管生成的miR-10b被有效抑制（P <0.001），有趣的是，调节血管生成的miR-126略有增加（P <0.05），但是其他miRNA，包括miR-31 ，miR-21，miR-101，miR-340，miR-29c，miR-206和miR-146a不受影响。此外，观察到一些血管生成诱导基因CDH5（P <0.001），FOXM1（P <0）的水平显着下降。芬维A胺处理的内皮细胞中的001）和eNOS（P <0.01和P <0.001）。我们的结果表明，fenretinide通过下调CDH5，FOXM1和eNOS基因并抑制miR-10b表现出抗血管生成活性。