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Published on: August 14, 2019
Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser
1Department of Surgery and Biomedical Engineering, Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, 92617, U.S.A; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
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.
Insights
Topical axitinib effectively suppresses pulsed dye laser-induced angiogenesis by inhibiting key signaling pathways. This finding offers a potential strategy to prevent port-wine stain blood vessel recurrence after treatment.
Area of Science:
- Dermatology
- Vascular Biology
- Pharmacology
Background:
- Port-wine stain (PWS) recurrence after pulsed dye laser (PDL) treatment is driven by PDL-induced angiogenesis.
- Overcoming this recurrence is crucial for improved PWS therapeutic outcomes.
Purpose of the Study:
- To investigate if topical axitinib can inhibit PDL-induced angiogenesis.
Main Methods:
- Examined mRNA expression of 86 angiogenic genes and protein phosphorylation (ERK, AKT, p70S6K) in rodent skin after PDL exposure.
- Assessed the effects of topical 0.5% axitinib on these markers and its skin penetration depth.
Main Results:
- PDL-induced angiogenic gene expression peaked at days 3-7 post-treatment.
- Topical axitinib significantly suppressed angiogenic gene upregulation and AKT, P70S6K, and ERK activation from days 1-7.
- Axitinib achieved a skin penetration depth of approximately 929.5 μm.
Conclusions:
- Topical axitinib effectively suppresses early-stage PDL-induced angiogenesis.
- Inhibition occurs via the AKT/mTOR/p70S6K and SH2D1A/MEK/ERK pathways.
- This suggests topical axitinib as a potential therapeutic agent for PWS treatment to prevent recurrence.
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