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

Jason Ko*, Joel Ross, Hani Awad, Herbert Hurwitz, Bruce Klitzman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalJournal of Surgical Research
Volume129
Issue number2
DOIs
StatePublished - Dec 1 2005

Keywords

  • Angiogenesis inhibitor
  • VEGF
  • Wound healing
  • ZD6474

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'The effects of ZD6474, an inhibitor of VEGF signaling, on cutaneous wound healing in mice'. Together they form a unique fingerprint.

Cite this