Blocking Wnt as a therapeutic target in mice model of skin cancer
| Autor: | Medhat Taha, Abdullah Alyoussef |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Skin Neoplasms
Carcinogenesis Croton Oil 9 10-Dimethyl-1 2-benzanthracene Cell Inflammation Antineoplastic Agents Dermatology SMAD 030207 dermatology & venereal diseases 03 medical and health sciences Mice 0302 clinical medicine Fibrosis medicine Animals Humans Croton oil Wnt Signaling Pathway integumentary system business.industry Wnt signaling pathway NF-kappa B General Medicine Neoplasms Experimental medicine.disease Gene Expression Regulation Neoplastic Wnt Proteins medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell Cancer research Cytokines medicine.symptom Skin cancer Drug Screening Assays Antitumor Epidermis business |
| Zdroj: | Archives of dermatological research. 311(8) |
| ISSN: | 1432-069X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink