The effects of ZD6474, an inhibitor of VEGF signaling, on cutaneous wound healing in mice.

Journal Article

BACKGROUND: ZD6474 is an inhibitor of the VEGFR-2 receptor tyrosine kinase with additional activity against EGFR-1 receptor tyrosine kinases that has been shown to inhibit tumor growth and wound-induced neovascularization in pre-clinical studies and phase I clinical trials. The purpose of this study was to determine the effects of ZD6474 on breaking strength in a murine model of cutaneous wound healing. MATERIALS AND METHODS: Balb/C mice were given ZD6474 (50 or 100 mg/kg p.o.) or vehicle starting 7 days before wounding. Two full-thickness incisions were made in each mouse and closed using suture. On post-wounding day 7 or 28, laser Doppler blood flow measurements were made, and the breaking strength of the wounded skin was determined. Microvessel density measurements were performed using computer image analysis of CD31-stained sections. RESULTS: Compared with controls, mice treated with ZD6474 showed a significantly reduced dose-dependent decline in breaking strength, both at POD 7 (P < 0.001) and at POD 28 (P < 0.005). Histologically, the ZD6474-treated mice showed a qualitative reduction in the degree of fibrosis and epithelial proliferation at the wound site, but no significant difference was noted between the 50 mg/kg and 100 mg/kg ZD6474-treated groups. Also, microvessel density measurements demonstrated no significant difference between groups. CONCLUSION: In a murine model of wound healing, ZD6474 treatment did not prevent wound healing, but was associated with a reduced skin breaking strength compared with vehicle-treated controls at both 7 and 28 days post-wounding. These observations may have clinical relevance for the perioperative management of patients treated with inhibitors of angiogenesis.

Full Text

Duke Authors

Cited Authors

  • Ko, J; Ross, J; Awad, H; Hurwitz, H; Klitzman, B

Published Date

  • December 2005

Published In

Volume / Issue

  • 129 / 2

Start / End Page

  • 251 - 259

PubMed ID

  • 16140331

International Standard Serial Number (ISSN)

  • 0022-4804

Digital Object Identifier (DOI)

  • 10.1016/j.jss.2005.05.006

Language

  • eng

Conference Location

  • United States