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Metformin is a Novel Suppressor for Vimentin in Human Gastric Cancer Cell Line
Shiva Valaee1, Mehdi Shamsara2, Mohammad Mehdi Yaghoobi1
1Research Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
Abstract:
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 in vivo studies can reveal metformin's potential in inhibition of EMT and metastasis of cancer cells.
Insights
Metformin effectively downregulates vimentin in gastric cancer cells, similar to vimentin-specific siRNA. This reduces cancer cell migration and invasion, suggesting metformin as a promising alternative for controlling metastasis.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Vimentin, an intermediate filament protein, is crucial for mesenchymal cells and is upregulated during epithelial-mesenchymal transition (EMT).
- Increased vimentin expression is linked to cancer metastasis, making it a target for therapeutic intervention.
- Current strategies to inhibit EMT markers involve drugs or small interfering RNA (siRNA).
Purpose of the Study:
- To investigate the efficacy of metformin in downregulating vimentin expression in AGS gastric cancer cells.
- To compare the effects of metformin with vimentin-specific siRNA (vim-siRNA) on vimentin levels and cancer cell behavior.
- To evaluate metformin as a potential alternative to siRNA for inhibiting gastric cancer cell migration and invasion.
Main Methods:
- AGS gastric cancer cells were treated with metformin and vim-siRNA for 48 hours.
- Vimentin downregulation was assessed using quantitative PCR and Western blot.
- Cell motility, migration, and invasion were analyzed using wound-healing and invasion assays.
Main Results:
- Metformin treatment resulted in vimentin downregulation comparable to that achieved with vim-siRNA.
- Both metformin and vim-siRNA significantly decreased the migration and invasion capabilities of AGS cells.
- This study is the first to show metformin's potential as an alternative to siRNA for inhibiting vimentin expression and cell migration.
Conclusions:
- Metformin serves as a viable alternative to vimentin-specific siRNA for inhibiting vimentin expression and reducing migration in AGS gastric cancer cells.
- Metformin offers potential advantages over siRNA due to its stability, cost-effectiveness, and simpler delivery.
- Further in vivo studies are warranted to explore metformin's therapeutic potential in inhibiting EMT and cancer metastasis.
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