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Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser

  • Author(s): Gao, L
  • Nadora, DM
  • Phan, S
  • Chernova, M
  • Sun, V
  • Preciado, SMO
  • Jia, W
  • Wang, G
  • Mihm, MC
  • Nelson, JS
  • Tan, W
  • et al.

Published Web Location

https://doi.org/10.1111/bjd.13439
Abstract

© 2014 British Association of Dermatologists. 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.

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