Combination of Decitabine and Entinostat Synergistically Inhibits Urothelial Bladder Cancer Cells via Activation of FoxO1
Abstract
:1. Introduction
2. Results
2.1. Combining DNMTi and HDACi Induces Synergistic Cytotoxicity in Urothelial Bladder Cancer Cell Lines
2.2. Combination Treatment of DAC and ENT Induces Apoptosis in Urothelial Bladder Cancer Cells Mediated by the Activation of Caspase 3/7
2.3. DAC Combined with ENT Affects the Cell Cycle Distribution in Urothelial Bladder Cancer Cells
2.4. DAC and ENT Alter RNA- and Protein-Expression and Protein Phosphorylation of Genes Involved in the Akt/FoxO Pathway
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. Cell Viability Assay
4.4. Synergistic Study
4.5. Apoptosis Assay
4.6. Cell Cycle Analysis
4.7. Caspase 3/7 Activation
4.8. Total RNA Extraction and RNA-seq Analysis
4.9. Analysis of RNA-Seq Data
4.10. Western Blot Analysis
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cell Lines | DAC | ENT | ||
---|---|---|---|---|
IC50 [µM] | pIC50 ± SEM | IC50 [µM] | pIC50 ± SEM | |
J82 | 30.5 | 4.52 ± 0.08 | 14.3 | 4.84 ± 0.06 |
J82CisR | 28.2 | 4.55 ± 0.18 | 15.6 | 4.81 ± 0.06 |
RT-112 | 0.22 | 6.65 ± 0.09 | 3.41 | 5.47 ± 0.11 |
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Wang, C.; Hamacher, A.; Petzsch, P.; Köhrer, K.; Niegisch, G.; Hoffmann, M.J.; Schulz, W.A.; Kassack, M.U. Combination of Decitabine and Entinostat Synergistically Inhibits Urothelial Bladder Cancer Cells via Activation of FoxO1. Cancers 2020, 12, 337. https://doi.org/10.3390/cancers12020337
Wang C, Hamacher A, Petzsch P, Köhrer K, Niegisch G, Hoffmann MJ, Schulz WA, Kassack MU. Combination of Decitabine and Entinostat Synergistically Inhibits Urothelial Bladder Cancer Cells via Activation of FoxO1. Cancers. 2020; 12(2):337. https://doi.org/10.3390/cancers12020337
Chicago/Turabian StyleWang, Chenyin, Alexandra Hamacher, Patrick Petzsch, Karl Köhrer, Günter Niegisch, Michèle J. Hoffmann, Wolfgang A. Schulz, and Matthias U. Kassack. 2020. "Combination of Decitabine and Entinostat Synergistically Inhibits Urothelial Bladder Cancer Cells via Activation of FoxO1" Cancers 12, no. 2: 337. https://doi.org/10.3390/cancers12020337