Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner
Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner
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DOI：
10.1158/1535-7163.mct-12-1226-t
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发表时间：
2013-08-01
影响因子：
5.7
通讯作者：
Rocchi, Stephane
中科院分区：
文献类型：
--
作者：
Cerezo, Michael;Tichet, Melanie;Rocchi, Stephane
据报道，二甲双胍抑制许多癌细胞的增殖，包括黑色素瘤细胞。在这份报告中，我们研究了二甲双胍对黑色素瘤侵袭和转移发展的影响。使用不同的体外方法，我们发现二甲双胍抑制细胞侵袭而不影响细胞迁移，并且与抗增殖作用无关。这种抑制与调节参与上皮-间充质转化的蛋白质如Slug、Snail、p53、纤连蛋白和N-钙粘蛋白的表达以及抑制MMP-2和MMP-9活化相关。此外，我们的数据表明，这一过程依赖于AMPK和肿瘤抑制蛋白p53的激活。最后，我们使用外渗和转移模型表明二甲双胍抑制小鼠黑色素瘤转移的发展。所提供的数据强化了二甲双胍可能是黑色素瘤治疗临床试验的良好候选药物的事实。（C）2013年AACR。
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.