Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. AKT Degrader and Inhibitor Treatment
2.3. Crispr-Cas9-Mediated Genome Editing
2.4. Immunoblotting
2.5. Cell Counting and Colony Formation Assay
2.6. Three-Dimensional Culture
2.7. Apoptosis Assay and Cell Cycle Analysis
2.8. Orthotopic Implantation and IVIS Imaging
2.9. RNA-Seq Analysis
2.10. Amplex Red Cholesterol Measurement Assay
2.11. RPPA
3. Results
3.1. AKT Degrader Was Superior to AKT Kinase Inhibitor in Slowing Pancreatic Cancer Cell Growth
3.2. Generation of KPC Cell Lines Deficient in AKT Isoforms by CRISPR-Cas9 Genome Editing
3.3. Genetic Deletion of Akt1/2/3 Significantly Impeded In Vitro PDAC Cell Growth
3.4. Genetic Ablation of Akt1/2/3 Slowed KPC Pancreatic Tumor Progression in a Syngeneic Orthotopic Implantation Mouse Model
3.5. Growth Effects of IGF-1-AKT Signaling in the KPC Cell Line and Role of Cholesterol Metabolism
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Chen, C.; Jiang, Y.-P.; You, I.; Gray, N.S.; Lin, R.Z. Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors. Cells 2024, 13, 1061. https://doi.org/10.3390/cells13121061
Chen C, Jiang Y-P, You I, Gray NS, Lin RZ. Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors. Cells. 2024; 13(12):1061. https://doi.org/10.3390/cells13121061
Chicago/Turabian StyleChen, Chuankai, Ya-Ping Jiang, Inchul You, Nathanael S. Gray, and Richard Z. Lin. 2024. "Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors" Cells 13, no. 12: 1061. https://doi.org/10.3390/cells13121061