Valaee Shiva, Shamsara Mehdi, Yaghoobi Mohammad Mehdi
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.
Int J Mol Cell Med. 2021 Summer;10(3):200-206. doi: 10.22088/IJMCM.BUMS.10.3.200. Epub 2022 Jan 10.
Vimentin, an intermediate filament of mesenchymal cells, is upregulated in epithelial-mesenchymal transition (EMT) and has a main role in cancer metastasis. As a new strategy to control metastatic outgrowth, EMT markers are generally inhibited using some drugs or specific siRNA. In this study, AGS gastric cancer cells were treated with metformin and vimentin-specific siRNA (vim-siRNA) for 48 h. The impact of metformin and vim-siRNA on vimentin downregulation in AGS cells were analyzed by quantitative PCR and Western blot. Following treatment with metformin and vim-siRNA, cell motility, migration and invasion abilities of AGS cells were also analyzed. The results showed that inhibition of vimentin due to metformin was comparable with the vim-siRNA. Furthermore, wound-healing and invasion assays showed a significant decrease in migration and invasion of AGS cells following metformin and vim-siRNA treatment. Our finding for the first time indicated that metformin can be an alternative to specific siRNA for inhibition of vimentin expression and migration of AGS cell line. Taken together, our data indicates that the use of metformin might have a priority to siRNA for inhibition of gastric cancer cell behaviors siRNA is more unstable and expensive than metformin, and needs special vehicles and delivery strategies for efficient transfection of cells. Further studies can reveal metformin's potential in inhibition of EMT and metastasis of cancer cells.
波形蛋白是间充质细胞的一种中间丝，在上皮-间质转化（EMT）过程中上调，在癌症转移中起主要作用。作为控制转移生长的一种新策略，通常使用一些药物或特异性小干扰RNA（siRNA）来抑制EMT标志物。在本研究中，用二甲双胍和波形蛋白特异性siRNA（vim-siRNA）处理AGS胃癌细胞48小时。通过定量PCR和蛋白质印迹分析二甲双胍和vim-siRNA对AGS细胞中波形蛋白下调的影响。在用二甲双胍和vim-siRNA处理后，还分析了AGS细胞的细胞运动性、迁移和侵袭能力。结果表明，二甲双胍对波形蛋白的抑制作用与vim-siRNA相当。此外，伤口愈合和侵袭试验表明，在二甲双胍和vim-siRNA处理后，AGS细胞的迁移和侵袭显著减少。我们的发现首次表明，二甲双胍可以替代特异性siRNA来抑制AGS细胞系中波形蛋白的表达和迁移。综上所述，我们的数据表明，在抑制胃癌细胞行为方面，使用二甲双胍可能比siRNA更具优势，因为siRNA比二甲双胍更不稳定、更昂贵，并且需要特殊的载体和递送策略才能有效地转染细胞。进一步的研究可以揭示二甲双胍在抑制癌细胞EMT和转移方面的潜力。
