Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Metabolic Features of MPM Cell Lines
2.2. The Combined Treatment with CDK4/6 and PI3K/mTOR Inhibitors Induces Additive or Synergistic Inhibitory Effects on Cell Proliferation in MPM Cells
2.3. The Combined Treatment with CDK4/6 and PI3K/mTOR Inhibitors Impairs Glucose Metabolism in MPM Cells
2.4. The Combined Treatment with CDK4/6 and PI3K/mTOR Inhibitors Inhibits Mitochondrial Respiration in MPM Cells
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Drug Treatment
4.3. Analysis of Cell Proliferation
4.4. Western Blotting
4.5. Metabolic Assays
4.5.1. Glucose Uptake and Consumption
4.5.2. OCR and ECAR Measurements
4.6. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
Abbreviations
MPM | Malignant Pleural Mesothelioma |
CDK | Cyclin-dependent kinase |
RB | Retinoblastoma Protein |
ECAR | extracellular acidification |
OCR | oxygen consumption rate |
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Bonelli, M.; Terenziani, R.; Zoppi, S.; Fumarola, C.; La Monica, S.; Cretella, D.; Alfieri, R.; Cavazzoni, A.; Digiacomo, G.; Galetti, M.; et al. Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells. Int. J. Mol. Sci. 2020, 21, 5165. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145165
Bonelli M, Terenziani R, Zoppi S, Fumarola C, La Monica S, Cretella D, Alfieri R, Cavazzoni A, Digiacomo G, Galetti M, et al. Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells. International Journal of Molecular Sciences. 2020; 21(14):5165. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145165
Chicago/Turabian StyleBonelli, Mara, Rita Terenziani, Silvia Zoppi, Claudia Fumarola, Silvia La Monica, Daniele Cretella, Roberta Alfieri, Andrea Cavazzoni, Graziana Digiacomo, Maricla Galetti, and et al. 2020. "Dual Inhibition of CDK4/6 and PI3K/AKT/mTOR Signaling Impairs Energy Metabolism in MPM Cancer Cells" International Journal of Molecular Sciences 21, no. 14: 5165. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145165