Lidocaine inhibits vascular endothelial growth factor-A-induced angiogenesis

• Published in: Journal of anesthesia Vol. 34; no. 6; pp. 857 - 864
• Main Authors: Suzuki, Shogo, Mori, Atsushi, Fukui, Aya, Ema, Yoshiaki, Nishiwaki, Kimitoshi
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.12.2020; Springer
• Subjects: Analysis; Anesthesiology; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Cell death; Cell Proliferation; Critical Care Medicine; Emergency Medicine; Ethylenediaminetetraacetic acid; Human Umbilical Vein Endothelial Cells; Humans; Intensive; Ischemia; Lidocaine; Lidocaine - pharmacology; Lidocaine - therapeutic use; Medicine; Medicine & Public Health; Neovascularization, Pathologic - drug therapy; Original Article; Pain Medicine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Japan; Ketamine; Anti-angiogenesis; Vascular endothelial growth factor A; Lidocaine
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-020-02830-7

Purpose Angiogenesis is closely related to the pathophysiology of diseases such as cancer or ischemia. Here, we investigated the effect of lidocaine at clinically effective blood concentrations on vascular endothelial growth factor A (VEGF-A)-induced angiogenesis. In addition, we aimed to clarify the mechanisms by which lidocaine could inhibit angiogenesis. Methods Angiogenesis was analyzed using commercially available in vitro assay kits in human umbilical vein endothelial cells (HUVECs)/normal human dermal fibroblast co-culture systems. The effects of lidocaine on cytotoxicity, VEGF-induced cell migration, and VEGF-induced cell proliferation were examined in HUVECs using lactate dehydrogenase cytotoxic, Boyden chamber, and WST-8 assays, respectively. The VEGF signaling pathway via VEGF receptor 2 (VEGFR-2) was analyzed by western blotting. Results Lidocaine elicited a significant dose-dependent, angiogenesis-inhibitory effect at a concentration range of 1–10 μg/ml. At this concentration range, cell death was not observed. Lidocaine, at a concentration of 10 μg/ml, significantly inhibited cell proliferation but not cell migration, induced by VEGF-A in HUVECs. Furthermore, lidocaine, in a dose-dependent manner, significantly inhibited the VEGF-A-induced phosphorylation of VEGFR-2 at 3 and 10 μg/ml. Conclusion We demonstrated that lidocaine has an anti-angiogenesis effect on clinically effective blood concentrations without causing cell death. This finding could represent a new avenue for future research into anesthesia, cancer-related analgesia, and revascularization therapy.