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Archives of Dermatological Research

, Volume 311, Issue 8, pp 595–605 | Cite as

Blocking Wnt as a therapeutic target in mice model of skin cancer

  • Abdullah AlyoussefEmail author
  • Medhat Taha
Original Paper

Abstract

Wnt pathway plays an important role in controlling metabolism in cancer cells. It acts as positive modulator for both cell inflammation, through activation of NFκB, and fibrosis, through activation of TGF-β. Therefore, the aim of this study is to investigate the therapeutic effects of blocking Wnt pathway by IWP12 on skin cancer by studying its effects on skin cancer-induced inflammation and fibrosis in a mice model of skin cancer. Skin cancer was induced by application of 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil on the dorsal skin of mice. Dorsal skin was removed for estimation of gene and protein expression of Wnt, β-catenin, SMAD, TGF-β, NFκB, TNF-α, IL-4 and IL-10. Part of the skin is stained with hematoxylin/eosin for assessment of cell structure. Treatment of mice with IWP12 completely blocked Wnt in skin cancer mice without affecting the control mice. Skin of tumorigenic mice showed marked skin hyperkeratosis, parakeratosis, acanthosis and dysplasia. Treatment with IWP12 markedly attenuated epidermal atypia and hyperplasia. In addition, IWP12 reduced expression of β-catenin, SMAD, TGF-β, NFκB and TNF-α associated with increase in the expression of IL-4 and IL-10. In conclusion, blocking Wnt production ameliorated skin cancer via blocking pro-inflammatory cytokines and enhancing the anti-inflammatory cytokines. Moreover, blocking Wnt attenuated skin cancer-induced activation of fibrosis pathway.

Keywords

β-Catenin Interleukin (IL)-4/10 Nuclear factor (NF)κB Transforming growth factor (TGF)-β Tumor necrosis factor (TNF)-α Wnt 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal Medicine (Dermatology), Faculty of MedicineUniversity of TabukTabukSaudi Arabia
  2. 2.Department of Anatomy and Embryology, College of MedicineMansoura UniversityMansouraEgypt

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