Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser. (1st March 2015) - Gao, L.
Summary: Background: The recurrence of port‐wine stain (PWS) blood vessels by pulsed dye laser (PDL)‐induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome. Objectives: To determine whether PDL‐induced angiogenesis can be suppressed by topical axitinib. Methods: The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure. Results: The PDL‐induced increased transcriptional levels of angiogenic genes peaked at days 3–7 post‐PDL exposure. Topical application of 0·5% axitinib effectively suppressed the PDL‐induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post‐PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929·5 μm. Conclusions: Topical application of 0·5% axitinib can systematically suppress the PDL‐induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein‐1/mitogen‐activated protein kinase kinase/ERK pathway cascades.