Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner.
Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner.
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DOI：
10.1371/journal.pone.0174486
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Shamsara M
中科院分区：
文献类型：
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作者：
Valaee S;Yaghoobi MM;Shamsara M
上皮-间充质转化（Epithelial-mesenchymal transition， EMT）是胚胎发育和癌细胞扩散的关键阶段，主要通过间充质标志物的上调和细胞的运动来识别。二甲双胍是一种用于治疗2型糖尿病的抗糖尿病药物。二甲双胍对几种癌症的EMT抑制作用已被研究；然而，它在胃癌中的作用尚不清楚。本研究旨在探讨二甲双胍对胃癌细胞emt相关基因的抑制作用以及对胃癌细胞迁移和侵袭的影响。此外，为了研究葡萄糖对二甲双胍介导的EMT抑制的影响，所有实验都是在两种葡萄糖水平下进行的，类似于非空腹血糖（7.8 mM）和高血糖（17.5 mM）的情况。结果显示，在两种葡萄糖浓度下，二甲双胍均可减少间充质标志物，包括vimentin和β-catenin，并诱导上皮标志物E-cadherin。此外，伤口愈合和侵袭试验显示，在两种葡萄糖水平下，二甲双胍治疗后细胞迁移和侵袭显著减少。总之，我们的研究结果表明，二甲双胍在模拟正常和高血糖的条件下强烈抑制胃癌细胞的EMT。
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.