Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland.
Service of Anaesthesia, Bellinzona Regional Hospital, Bellinzona, Switzerland.
Br J Anaesth. 2018 Oct;121(4):962-968. doi: 10.1016/j.bja.2018.07.015. Epub 2018 Aug 16.
The metastatic potential of breast cancer cells has been strongly associated with overexpression of the chemokine CXCL12 and the activity of its receptor CXCR4. Lidocaine, a local anaesthetic that can be used during breast cancer excision, inhibits the growth, invasion, and migration of cancer cells. We therefore investigated, in a breast cancer cell line, whether lidocaine can modulate CXCL12-induced responses.
Intracellular calcium, cytoskeleton remodelling, and cell migration were assessed in vitro in MDA-MB-231 cells, a human breast cancer epithelial cell line, after exposure to lidocaine (10 μM or 100 μM).
Lidocaine (10 or 100 μM) significantly inhibited CXCR4 signalling, resulting in reduced calcium release (Fluo 340 nm/380 nm, 0.76 mean difference, p<0.0001), impaired cytoskeleton remodelling (F-Actin fluorescence mean intensity, 21 mean difference, P=0.002), and decreased motility of cancer cells, both in the scratch wound assay (wound area at 21 h, -19%, P<0.0001), and in chemotaxis experiments (fluorescence mean intensity, 0.16, P=0.0047). The effect of lidocaine was not associated with modulation of the CD44 adhesion molecule.
At clinical concentrations, lidocaine significantly inhibits CXCR4 signalling. The results presented shed new insights on the molecular mechanisms governing the inhibitory effect of lidocaine on cell migration.
乳腺癌细胞的转移潜能与趋化因子 CXCL12 的过表达及其受体 CXCR4 的活性密切相关。利多卡因是一种可在乳腺癌切除术中使用的局部麻醉剂，可抑制癌细胞的生长、侵袭和迁移。因此，我们在乳腺癌细胞系中研究了利多卡因是否可以调节 CXCL12 诱导的反应。
在 MDA-MB-231 细胞（一种人乳腺癌上皮细胞系）中，检测细胞内钙离子、细胞骨架重塑和细胞迁移，这些细胞在暴露于利多卡因（10 μM 或 100 μM）后。
利多卡因（10 或 100 μM）显著抑制 CXCR4 信号，导致钙释放减少（Fluo 340nm/380nm，0.76 均值差异，p<0.0001），细胞骨架重塑受损（F-肌动蛋白荧光平均强度，21 均值差异，P=0.002），以及癌细胞的迁移能力下降，划痕实验（21 小时时的伤口面积，-19%，P<0.0001）和趋化实验（荧光平均强度，0.16，P=0.0047）。利多卡因的作用与 CD44 黏附分子的调节无关。
在临床浓度下，利多卡因显著抑制 CXCR4 信号。研究结果为利多卡因抑制细胞迁移的分子机制提供了新的见解。
