期刊
MOLECULAR CANCER THERAPEUTICS
卷 12, 期 8, 页码 1605-1615出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-12-1226-T
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- INSERM
- University of Nice Sophia-Antipolis
- ARC [SFI 20121205378]
- INCA Recherche Translationnelle
- Societe Francaise de Dermatologie
- Ministere de l'Enseignement Superieur et de la Recherche
- Contrat Hospitalier de Recherche Translationnelle du CHU de Nice
Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without affecting cell migration and independently of antiproliferation action. This inhibition is correlated with modulation of expression of proteins involved in epithelial-mesenchymal transition such as Slug, Snail, SPARC, fibronectin, and N-cadherin and with inhibition of MMP-2 and MMP-9 activation. Furthermore, our data indicate that this process is dependent on activation of AMPK and tumor suppressor protein p53. Finally, we showed that metformin inhibits melanoma metastasis development in mice using extravasation and metastasis models. The presented data reinforce the fact that metformin might be a good candidate for clinical trial in melanoma treatment. (C)2013 AACR.
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