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 μM or 100 μM).
RESULTS 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.
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.
D'Agostino, G