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

Abstract

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.

Key points

• IGF-1/IGF-R1is highly expressed in different cancers as skin cancer.

• Blocking IGF-R1 production ameliorated skin cancer.

• Blocking IGF-R1 attenuated skin cancer-induced activation of tumor invasion markers.

GRAPHICAL ABSTRACT

Keywords:

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

Disclosure statement

No potential conflict of interest was reported by the authors.