Metformin blocks melanoma invasion and metastasis development in a AMPK/p53-dependent manner
Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel la metformine inhibe le processus métastatique d'un mélanome
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 anti-proliferation 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. Further our data indicate that this process is dependent of activation of AMPK and tumor suppressor protein, p53. Finally, we demonstrated 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.
http://mct.aacrjournals.org/content/early/2013/06/05/1535-7163.MCT-12-1226-T.abstract