Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration

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 mu M or 100 mu M).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, P = 0.002), and decreased motility of cancer cells, both in the scratch wound assay (wound area at 21 h, similar to 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.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.