期刊
MOLECULAR CANCER
卷 13, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1476-4598-13-264
关键词
Na(V)1.5 voltage-gated sodium channels; Cancer cell invasiveness; Ranolazine; Metastases
资金
- Ministere de la Recherche et des Technologies
- Inserm
- Ligue Nationale Contre le Cancer
- Region Centre (grant NaVMetarget)
- Region Centre (LIPIDS project of ARD-Biomedicaments)
- Association CANCEN
Background: Na(V)1.5 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, Na(V)1.5 activity promotes the proteolytic degradation of the extracellular matrix and enhances cell invasiveness. Findings: In this study, we showed that the extinction of Na(V)1.5 expression in human breast cancer cells almost completely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated that ranolazine (50 mu M) inhibited Na(V)1.5 currents in breast cancer cells and reduced Na(V)1.5-related cancer cell invasiveness in vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by Na(V)1.5-expressing human breast cancer cells. Conclusions: Taken together, our results demonstrate the importance of Na(V)1.5 in the metastatic colonisation of organs by breast cancer cells and indicate that small molecules interfering with Na-V activity, such as ranolazine, may represent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments.
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