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二甲双胍通过抑制上皮-间充质转化减少小鼠黑色素瘤肺转移。

Epithelial-mesenchymal transition inhibition by metformin reduces melanoma lung metastasis in a murine model.

机构信息

Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil.

出版信息

Sci Rep. 2022 Oct 22;12(1):17776. doi: 10.1038/s41598-022-22235-8.

Abstract

Melanoma is an aggressive cancer with fast metastatic spread and reduced survival time. One common event during the neoplastic progression is the epithelial-mesenchymal transition (EMT), which enhances invasiveness, cell migration, and metastasis. In this study, we investigated the effects of metformin at EMT in melanoma cell lines B16-F10 and A-375, in vitro, and the impact of EMT downregulation on melanoma progression in vivo. The metformin cells treatment reduces the migration potential in vitro and reduced the development of pulmonary metastases and the expressions of N-cadherin, vimentin, ZEB1, and ZEB2 at the metastases site, in vivo. These results indicate that metformin can promote EMT downregulation impairing the metastatic potential of melanoma cells.

摘要

黑色素瘤是一种侵袭性癌症,具有快速转移和降低生存时间的特点。在肿瘤进展过程中,上皮-间充质转化(EMT)是一种常见事件,它增强了侵袭性、细胞迁移和转移。在这项研究中,我们研究了二甲双胍在黑色素瘤细胞系 B16-F10 和 A-375 中的 EMT 作用,体外,并研究了 EMT 下调对体内黑色素瘤进展的影响。二甲双胍细胞处理减少了体外迁移潜能,并减少了肺转移的发展和转移部位的 N-钙粘蛋白、波形蛋白、ZEB1 和 ZEB2 的表达。这些结果表明,二甲双胍可以促进 EMT 下调,损害黑色素瘤细胞的转移潜能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30d1/9588059/5f0ea0766a3b/41598_2022_22235_Fig1_HTML.jpg

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