Open Access

Vandetanib and ADAM inhibitors synergistically attenuate the pathological migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF-mediated MAPK pathway

  • Authors:
    • Daejin Kim
    • Hyun‑Suk Ko
    • Ga Bin Park
    • Dae Young Hur
    • Yeong Seok Kim
    • Jae Wook Yang
  • View Affiliations

  • Published online on: February 8, 2017     https://doi.org/10.3892/etm.2017.4110
  • Pages: 1415-1425
  • Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The extracellular signals induced by vascular endothelial growth factor (VEGF) are implicated in choroidal neovascularization (CNV) and thus, are associated with vision‑limiting complications in the human retina. Vandetanib is an oral anticancer drug that selectively inhibits the activities of VEGF receptor and epidermal growth factor receptor tyrosine kinase; however, the effects of vandetanib on VEGF in retinal pigment epithelial (RPE) cells have not yet been studied. In the present study, a combined treatment of vandetanib and a disintegrin and metalloproteinase (ADAM) protein inhibitors were used to assess the regulation of Epstein‑Barr virus (EBV)‑infected ARPE19 cells (ARPE19/EBV) migration as a model of CNV. Vandetanib suppressed the expression of the mesenchymal markers ADAM10 and ADAM17 in ARPE19/EBV cells, and also upregulated epithelial cell markers of the RPE cells, E‑cadherin and N‑cadherin. The migratory activity of ARPE19/EBV induced by VEGF was efficiently blocked by vandetanib. Furthermore, co‑treatment with vandetanib and an ADAM10 inhibitor (GI254023X) or ADAM17 inhibitor (Marimastat) synergistically prevented migration and the expression of vimentin, Snail and α‑smooth muscle actin by regulating extracellular signal‑regulated kinase and p38 mitogen-activated protein kinase. These results suggest that a combination treatment of vandetanib and ADAM inhibitors may be developed as a novel therapeutic regimen to control retina neovascular disease.
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April-2017
Volume 13 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Kim D, Ko HS, Park GB, Hur DY, Kim YS and Yang JW: Vandetanib and ADAM inhibitors synergistically attenuate the pathological migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF-mediated MAPK pathway. Exp Ther Med 13: 1415-1425, 2017
APA
Kim, D., Ko, H., Park, G.B., Hur, D.Y., Kim, Y.S., & Yang, J.W. (2017). Vandetanib and ADAM inhibitors synergistically attenuate the pathological migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF-mediated MAPK pathway. Experimental and Therapeutic Medicine, 13, 1415-1425. https://doi.org/10.3892/etm.2017.4110
MLA
Kim, D., Ko, H., Park, G. B., Hur, D. Y., Kim, Y. S., Yang, J. W."Vandetanib and ADAM inhibitors synergistically attenuate the pathological migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF-mediated MAPK pathway". Experimental and Therapeutic Medicine 13.4 (2017): 1415-1425.
Chicago
Kim, D., Ko, H., Park, G. B., Hur, D. Y., Kim, Y. S., Yang, J. W."Vandetanib and ADAM inhibitors synergistically attenuate the pathological migration of EBV-infected retinal pigment epithelial cells by regulating the VEGF-mediated MAPK pathway". Experimental and Therapeutic Medicine 13, no. 4 (2017): 1415-1425. https://doi.org/10.3892/etm.2017.4110