G D'Agostino1, A Saporito2, V Cecchinato3, Y Silvestri3, A Borgeat4, L Anselmi5, M Uguccioni6. 1. Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland. Electronic address: gianluca.dagostino@irb.usi.ch. 2. Service of Anaesthesia, Bellinzona Regional Hospital, Bellinzona, Switzerland. Electronic address: andrea.saporito@eoc.ch. 3. Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland. 4. Universitaetsklinik Balgrist, University of Zurich, Zurich, Switzerland. 5. Service of Anaesthesia, Bellinzona Regional Hospital, Bellinzona, Switzerland. 6. Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera italiana, Bellinzona, Switzerland; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan, Italy.
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.
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 humanbreast 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.
Authors: Beom Seok Han; Kyung Hee Jung; Ji Eun Lee; Young-Chan Yoon; Soyeon Ko; Min Seok Park; Yun Ji Lee; Sang Eun Kim; Ye Jin Cho; Pureunchowon Lee; Joo Han Lim; Eunsoo Jang; Hyunzu Kim; Soon-Sun Hong Journal: Am J Cancer Res Date: 2022-07-15 Impact factor: 5.942