Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1
Abstract
:1. Introduction
2. Results
2.1. Metformin and DCA Effectively Induced Apoptosis in Liver Cancer Cells
2.2. Metformin Sensitized Liver Cancer Cells to DCA through Increasing Glycolysis
2.3. Metformin and DCA Effectively Suppressed mTORC1 Expression by Inhibiting PI3K/Akt/mTORC1 Signaling and Upregulating REDD1
2.4. Modulating ROS Is Important for Anticancer Effects of the Metformin and DCA Treatment
2.5. Anticancer Effect of a Combination Treatment of Metformin and DCA in Murine Models
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Chemicals
4.2. Cell Viability Assay
4.3. Western Blot Analysis
4.4. Flow Cytometry with Annexin V-FITC Staining
4.5. Extracellular Lactate Assay and Intracellular ATP Assay
4.6. Assessment of Intracellular and Mitochondrial Reactive Oxygen Species Generation
4.7. In Vivo Subcutaneous Xenograft Model
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Kim, T.S.; Lee, M.; Park, M.; Kim, S.Y.; Shim, M.S.; Lee, C.Y.; Choi, D.H.; Cho, Y. Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1. Int. J. Mol. Sci. 2021, 22, 10027. https://doi.org/10.3390/ijms221810027
Kim TS, Lee M, Park M, Kim SY, Shim MS, Lee CY, Choi DH, Cho Y. Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1. International Journal of Molecular Sciences. 2021; 22(18):10027. https://doi.org/10.3390/ijms221810027
Chicago/Turabian StyleKim, Tae Suk, Minjong Lee, Minji Park, Sae Yun Kim, Min Suk Shim, Chea Yeon Lee, Dae Hee Choi, and Yuri Cho. 2021. "Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1" International Journal of Molecular Sciences 22, no. 18: 10027. https://doi.org/10.3390/ijms221810027
APA StyleKim, T. S., Lee, M., Park, M., Kim, S. Y., Shim, M. S., Lee, C. Y., Choi, D. H., & Cho, Y. (2021). Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1. International Journal of Molecular Sciences, 22(18), 10027. https://doi.org/10.3390/ijms221810027