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Fenretinide reduces angiogenesis by downregulating CDH5, FOXM1 and eNOS genes and suppressing microRNA-10b

  • Elif Isil Yücel
  • Mehmet SahinEmail author
Original Article
  • 60 Downloads

Abstract

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.

Keywords

Fenretinide Angiogenesis CDH5 eNOS FOXM1 miRNA 

Notes

Funding

Funding for this study was provided by grants from Gaziantep University Scientific Research Project Unit (Project Number: TF.YLT.18.43). Also this study was supported by Gaziantep University Health Sciences Institute.

Compliance with ethical standards

Conflict of interest

We declare that all authors have no potential conflict of interest.

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© Springer Nature B.V. 2020

Authors and Affiliations

  1. 1.Department of Medical Biology, Faculty of MedicineGaziantep UniversityGaziantepTurkey

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