A multitargeted receptor tyrosine kinase inhibitor, SU6668, does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.
Disturbances of angiogenesis have been suggested to result in the impaired healing of skin wounds. Using a murine incisional wound model, we evaluated the effects of SU6668, an inhibitor of the receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), on the healing of skin wounds. Mice were administered vehicle, SU6668 (100 or 400 mg/kg/day, b.i.d.), or dexamethasone (1 mg/kg/day, b.i.d.), and wound healing was monitored histologically and using a tensiometer. SU6668 at a fully efficacious dose of 100 mg/kg/day had no significant effect on the healing process, while at a supratherapeutic dose of 400 mg/kg/day, there were subtle transient histologic changes and slight decreases in tensile strength, suggesting a slight delay in the wound healing process. In conclusion, these data indicate that inhibition of the receptors for VEGF, PDGF, and FGF at levels necessary to inhibit tumor growth in mouse xenograft models does not affect the healing of incisional wounds in mice. Redundant pathways likely compensate for inhibition of VEGF, PDGF, and FGF signaling pathways in the skin healing process.
Duan
W Rachel
WR
Pharmacia Corp., Skokie, IL, USA. w.rachel.duan@pfizer.com
Patyna
Shem
S
Kuhlmann
Madeline A
MA
Li
Shuanglian
S
Blomme
Eric A G
EA
D000818:Animals; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012867:Skin / Q000293:injuries* / Q000473:pathology; D013718:Tensile Strength / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
D007211:Indoles; D000078183:Oxindoles; D011422:Propionates; D011758:Pyrroles; D017468:Receptors, Fibroblast Growth Factor; D003907:Dexamethasone; C412603:orantinib; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor