SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice

Jin-hong Park; Seung-Hee Ryu; Eun Kyung Choi; Seung Do Anh; Euisun Park; Kyung-Chul Choi; Sang-wook Lee

doi:10.18632/oncotarget.2878

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Research Papers:

SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice

Jin-hong Park _, Seung-Hee Ryu, Eun Kyung Choi, Seung Do Anh, Euisun Park, Kyung-Chul Choi and Sang-wook Lee

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Oncotarget. 2015; 6:4171-4179. https://doi.org/10.18632/oncotarget.2878

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Abstract

Jin-hong Park1, Seung-Hee Ryu1, Eun Kyung Choi1, Seung Do Ahn1, Euisun Park3, Kyung-Chul Choi2,*, Sang-wook Lee1,*

1Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

2Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea

3Life Science Research Center, SK Chemicals, Seongnam-si, Korea

*These authors have contributed equally to this work

Correspondence to:

Sang-wook Lee, e-mail: [email protected]

Kyung-Chul Choi, e-mail: [email protected]

Keywords: Radiation, Fibrosis, TGF-β1, ALK5, SKI2162

Received: September 17, 2014 Accepted: December 08, 2014 Published: February 17, 2015

ABSTRACT

Here we demonstrated that SKI2162, a small-molecule inhibitor of the TGF-β type I receptor (ALK5), prevented radiation-induced fibrosis (RIF) in mice. SKI2162 inhibited phosphorylation of Smad and induction of RIF-related genes in vitro. In RIF a mouse model, SKI2162 reduced late skin reactions and leg-contracture without jeopardizing the acute skin reaction. Irradiation of mouse tissue increased COL1A2 mRNA levels, and topical administration of SKI2162 significantly inhibited this effect. Thus, these findings support that SKI2162 has potential value as novel RIF-protective agent, and could be candidate for clinical trials.

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Research Papers:

SKI2162, an inhibitor of the TGF-β type I receptor (ALK5), inhibits radiation-induced fibrosis in mice

Abstract