Sevoflurane inhibits growth factor-induced angiogenesis through suppressing Rac1/paxillin/FAK and Ras/Akt/mTOR

Abstract

Aim: We investigated the direct effects of sevoflurane on angiogenesis and a variety of tumor cells. Materials & methods: The antiangiogenic activity of sevoflurane was determined using angiogenesis and biochemical assays. Results: Sevoflurane at low doses inhibits capillary network formation. Sevoflurane inhibited VEGF- and bFGF-stimulated migration, adhesion and growth in endothelial cells and induced apoptosis. Sevoflurane only at high doses inhibited growth and migration of tumor cells, suggesting differential effects of sevoflurane between endothelial and tumor cells. Mechanistically, sevoflurane decreased growth factors-induced Ras and Rac1 activation, and suppressed Ras and Rac1 signaling. Conclusion: We demonstrate the antiangiogenic effects of sevoflurane and provide preclinical evidence into the potential mechanisms by which sevoflurane may negatively affect cancer growth and metastasis.