Department of Anesthesiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts & Science, Xiangyang, Hubei Province 441021, PR China.
Future Oncol. 2020 Aug;16(22):1619-1627. doi: 10.2217/fon-2020-0221. Epub 2020 Jun 1.
We investigated the direct effects of sevoflurane on angiogenesis and a variety of tumor cells. The antiangiogenic activity of sevoflurane was determined using angiogenesis and biochemical assays. 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. 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.
我们研究了七氟醚对血管生成和多种肿瘤细胞的直接影响。通过血管生成和生化测定来确定七氟醚的抗血管生成活性。低剂量的七氟醚抑制毛细血管网络的形成。七氟醚抑制血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)刺激的内皮细胞迁移、黏附和生长，并诱导细胞凋亡。只有高剂量的七氟醚才抑制肿瘤细胞的生长和迁移，提示七氟醚对内皮细胞和肿瘤细胞的作用存在差异。在机制上，七氟醚降低了生长因子诱导的 Ras 和 Rac1 的激活，并抑制了 Ras 和 Rac1 信号通路。我们证明了七氟醚的抗血管生成作用，并提供了七氟醚可能通过负性影响肿瘤生长和转移的潜在机制的临床前证据。
