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.

Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration

Uguccioni, M
2018-01-01

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 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.
2018
CXCL12
CXCR4
breast cancer
cell migration
lidocaine
Anesthetics, Local
Breast Neoplasms
Calcium
Cell Line, Tumor
Cell Movement
Chemokine CXCL12
Chemotaxis
Cytoskeleton
Female
Humans
Lidocaine
MCF-7 Cells
Receptors, CXCR4
Signal Transduction
Wounds and Injuries
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/59427
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