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二甲双胍通过以不依赖葡萄糖的方式抑制上皮-间质转化来抑制胃癌细胞的转移特性。

Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner.

作者信息

Valaee Shiva, Yaghoobi Mohammad Mehdi, Shamsara Mehdi

机构信息

Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.

Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

出版信息

PLoS One. 2017 Mar 23;12(3):e0174486. doi: 10.1371/journal.pone.0174486. eCollection 2017.

DOI:10.1371/journal.pone.0174486
PMID:28334027
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5363973/
Abstract

Epithelial-mesenchymal transition (EMT), which is mainly recognized by upregulation of mesenchymal markers and movement of cells, is a critical stage occurred during embryo development and spreading cancerous cells. Metformin is an antidiabetic drug used in treatment of type 2 diabetes. EMT inhibitory effect of metformin has been studied in several cancers; however, it remains unknown in gastric cancer. The aim of the present study was to investigate the metformin effects on inhibition of EMT-related genes as well as migration and invasion of AGS gastric cancer cell line. Moreover, to study the effect of glucose on metformin-mediated EMT inhibition, all experiments were performed in two glucose levels, similar to non-fasting blood sugar (7.8 mM) and hyperglycemic (17.5 mM) conditions. The results showed reduction of mesenchymal markers, including vimentin and β-catenin, and induction of epithelial marker, E-cadherin, by metformin in both glucose concentrations. Furthermore, wound-healing and invasion assays showed a significant decrease in cell migration and invasion after metformin treatment in both glucose levels. In conclusion, our results indicated that metformin strongly inhibited EMT of gastric cancer cells in conditions mimicking normo and hyperglycemic blood sugar.

摘要

上皮-间质转化（EMT）主要通过间充质标志物的上调和细胞移动来识别，是胚胎发育和癌细胞扩散过程中出现的一个关键阶段。二甲双胍是一种用于治疗2型糖尿病的抗糖尿病药物。二甲双胍对EMT的抑制作用已在多种癌症中进行了研究；然而，在胃癌中的情况仍不清楚。本研究的目的是探讨二甲双胍对AGS胃癌细胞系中EMT相关基因以及迁移和侵袭的抑制作用。此外，为了研究葡萄糖对二甲双胍介导的EMT抑制的影响，所有实验均在两种葡萄糖水平下进行，类似于非空腹血糖（7.8 mM）和高血糖（17.5 mM）条件。结果显示，在两种葡萄糖浓度下，二甲双胍均可降低包括波形蛋白和β-连环蛋白在内的间充质标志物，并诱导上皮标志物E-钙黏蛋白的表达。此外，伤口愈合和侵袭试验表明，在两种葡萄糖水平下，二甲双胍处理后细胞迁移和侵袭均显著降低。总之，我们的结果表明，在模拟正常血糖和高血糖的条件下，二甲双胍强烈抑制胃癌细胞的EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/fca48bab96c8/pone.0174486.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/96b66056235d/pone.0174486.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/ad6b79f79ede/pone.0174486.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/60e48050719a/pone.0174486.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/fca48bab96c8/pone.0174486.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/96b66056235d/pone.0174486.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/ad6b79f79ede/pone.0174486.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/60e48050719a/pone.0174486.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a0/5363973/fca48bab96c8/pone.0174486.g004.jpg

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