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AB0168 Therapeutic effects of sunitinib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a murine arthritis model
  1. K. Furuya1,
  2. Y. Kaku1,
  3. K. Yoshida2,
  4. K. Joh3,
  5. D. Kurosaka1
  1. 1Rheumatology, Jikei University School of Medicine, Tokyo, Japan
  2. 2Rheumatology, University of Michigan, Michigan, United States
  3. 3Pathology, Sendai Shakai Hoken Hospital, Miyagi, Japan

Abstract

Background Angiogenesis, the formation of new blood vessels, is recently considered as a key event and a therapeutic target of the pannus formation in rheumatoid arthritis1).

Objectives The purpose of this study was to confirm the inhibitory effects of sunitinib, an angiogenesis inhibitor that targets vascular endothelial growth factor receptor (VEGFR) tyrosine kinase2), on arthritis in mice with type II collagen-induced arthritis (CIA).

Methods Sunitinib at 30 or 60 mg/kg/day was intraperitoneally administered to mice with CIA. We compared the arthritis score, pathological score, bone density, and synovial microvascular density between the control and treatment groups.

Results In the sunitinib-treated groups, the arthritis score decreased in a dose-dependent manner in comparison with the control group. Furthermore, improvement in the pathological score, inhibition of loss in the bone density, and a decrease in the synovial microvascular density were noted.

Conclusions An angiogenesis inhibitor, sunitinib, inhibited arthritis in a murine CIA model. This compound may be useful for treating arthritis.

  1. Szekanecz Z, Koch AE. Angiogenesis and its targeting in rheumatoid arthritis. Vascular pharmacology 2009 Jul;51(1):1-7.

  2. Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clinical cancer research: an official journal of the American Association for Cancer Research 2003 Jan;9(1):327-331

Disclosure of Interest None Declared

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