Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization

Molecular Cancer

Short Communication

Christine Collin¹  Jean-Christophe Pagès²  Thibauld Oullier³  Séverine Marionneau-Lambot³  Virginie Joulin⁴  Jean-Yves Le Guennec⁵  Ludovic Gillet⁶  Emeline Bon⁶  Virginie Driffort⁶  Marie-Lise Jourdan⁷  Philippe Bougnoux⁷  Pierre Besson⁸  Stéphan Chevalier⁸  Sébastien Roger⁹ 

[1]CHRU de Tours, Tours, France

[2]CHRU de Tours, Tours, France

[3]Inserm, U966, Université François-Rabelais de Tours, Tours, France

[4]Cancéropôle du Grand Ouest, Nantes, France

[5]Inserm U1009, Institut Gustave Roussy, Villejuif, France

[6]Inserm U1046, Université de Montpellier-1, Université de Montpellier-2, Montpellier, France

[7]Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, 10 Boulevard Tonnellé, 37032, Tours, France

[8]Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, 10 Boulevard Tonnellé, 37032, Tours, France

[9]CHRU de Tours, Tours, France

[10]Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, 10 Boulevard Tonnellé, 37032, Tours, France

[11]UFR Sciences Pharmaceutiques, Université François-Rabelais de Tours, Tours, France

[12]Inserm UMR1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, 10 Boulevard Tonnellé, 37032, Tours, France

[13]UFR Sciences et Techniques, Département de Physiologie Animale, Université François-Rabelais de Tours, Tours, France

关键词: Na1.5 voltage-gated sodium channels;    Cancer cell invasiveness;    Ranolazine;    Metastases;   

DOI  :  10.1186/1476-4598-13-264

 received in 2014-08-28, accepted in 2014-12-03,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundNaV1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expression level is associated with metastatic occurrence and patients’ death. In breast cancer cells, NaV1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness.FindingsIn this study, we showed that the extinction of NaV1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 μM) inhibited NaV1.5 currents in breast cancer cells and reduced NaV1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by NaV1.5-expressing human breast cancer cells.ConclusionsTaken together, our results demonstrate the importance of NaV1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with NaV activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.

【 授权许可】

Unknown   
© Driffort et al.; licensee BioMed Central. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.