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Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration


D'Agostino, G; Saporito, A; Cecchinato, V; Silvestri, Y; Borgeat, A; Anselmi, L; Uguccioni, M (2018). Lidocaine inhibits cytoskeletal remodelling and human breast cancer cell migration. British Journal of Anaesthesia, 121(4):962-968.

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:October 2018
Deposited On:02 Oct 2018 14:03
Last Modified:24 Sep 2019 23:48
Publisher:Elsevier
ISSN:0007-0912
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.bja.2018.07.015
PubMed ID:30236259

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