利多卡因可抑制细胞骨架重塑和人类乳腺癌细胞迁移
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Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration.
背景与目的
乳腺癌细胞的转移潜能与趋化因子CXCL12的过表达和其受体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。
方 法
在暴露于利多卡因（10μM或100μM）后，以人乳腺癌上皮细胞系MDA-MB-231细胞在体外评估细胞内钙水平、细胞骨架重塑和细胞迁移。
结 果
利多卡因（10或100μM）显着抑制CXCR4信号传导，导致钙释放减少（Fluo 340 nm / 380 nm，平均差异0.76，p <0.0001），细胞骨架重塑受损和趋化性实验（荧光平均强度，0.16，P = 0.0047）中，癌细胞的活动性均降低。 利多卡因的作用与CD44粘附分子的调节无关。
结 论
在临床浓度下，利多卡因显着抑制CXCR4信号传导。我们所提出的结果为控制利多卡因对细胞迁移的抑制作用的分子机制提供了新的见解。
原始文献摘要
G. D’Agostino1, A. Saporito2, V. Cecchinato1 , et al. Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration.[B]. British Journal of Anaesthesia,1e7 (2018) ,doi: 10.1016/j.bja.2018.07.015
Abstract Background: 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. Methods: 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 mM or 100 mM). Results: Lidocaine (10 or 100 mM) 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, P¼0.002), 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, P¼0.0047). The effect of lidocaine was not associated with modulation of the CD44 adhesion molecule. Conclusions: 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.
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贵州医科大学高鸿教授课题组
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