4.3 Article

The therapeutic effects of blocking IGF-R1 on mice model of skin cancer

Journal

JOURNAL OF DERMATOLOGICAL TREATMENT
Volume 32, Issue 7, Pages 803-811

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/09546634.2019.1708243

Keywords

Fascin-1; glypican-3 (GPC3); insulin-like growth factor (IGF)-1; insulin-like growth factor receptor (IGF-R1); matrix metalloproteinase (MMP9); syndecan-1

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The study investigated the therapeutic effects of blocking the IGF-R1 pathway with PQ401 in experimental skin cancer induced in mice. Results showed that PQ401 reduced tumor growth, improved skin lesions, and decreased expression of tumor invasion markers in skin cancer.
Background and objectives: The incidence of skin cancer has raised in the last few years. One of the important growth factors found in the skin layers is insulin-like growth factor (IGF)-1. It is directly linked with many cancers in different organs. Therefore, we aimed to explore the therapeutic effects of blocking IGF-1 receptor (IGF-R1) pathway by PQ401 in skin cancer as well as studying its effect on tumor invasion markers. Materials and methods: We experimentally induced skin cancer in mice by the application of 7,12-dimethylbenz (a) anthracene. Skin samples were removed for determination of gen and protein expression of IGF-1, IGF-R1, glypican-3, MMP9, syndecan-1 and fascin-1 by Western blot and PCR. Moreover, skin sections were stained with hematoxylin/eosin and Mallory. Results: Treatment with PQ401 blocked the expression of IGF-R1 in the skin, which is associated with reduction in the skin cancer-induced tumors and scratches. In addition, PQ401 ameliorated skin cancer induced formation of epidermal atypia and hyperplasia. PQ401 reduced both gene and protein expression of the tumor invasion markers, MMP9, syndecan-1 and fascin-1, without affecting gene and protein expression of glypican-3 and IGF-1 in skin cancer group. Conclusion: Blocking IGF-R1 has therapeutic effects against experimental skin cancer induced in mice. In addition, blocking IGF = R1 attenuated skin cancer-induced activation of tumor invasion markers.

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