Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser. (1st March 2015)

• Record Type: Journal Article
• Authors: Gao, L.; Nadora, D.M.; Phan, S.; Chernova, M.; Sun, V.; Preciado, S.M.O.; Jia, W.; Wang, G.; Mihm, M.C.; Nelson, J.S.; Tan, W.
• Is Part Of: British journal of dermatology. Volume 172:Number 3(2015:Mar.)
• Page Start: 669
• Page End: 676
• Publication Date: 2015-03-01
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13439
• Languages: English
• ISSNs: 0007-0963

Abstract

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.