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

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.

journal_name

Arch Dermatol Res

authors

Alyoussef A,Taha M

doi

10.1007/s00403-019-01939-4

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

595-605

issue

8

eissn

0340-3696

issn

1432-069X

pii

10.1007/s00403-019-01939-4

journal_volume

311

pub_type

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