Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture and Reagents
2.2. Cell Proliferation Assays
2.3. Drug Synergy Assay
2.4. Lentivirus Packaging and Cell Transfection
2.5. RNA Extraction and Quantitative Real-Time PCR (PCR) Analysis
2.6. Western Blot and Protein Stability Analysis
2.7. Immunoprecipitation (IP)
2.8. Reactive oxygen species (ROS) Measurement
2.9. In Vitro Deubiquitinating Enzymes (DUB) Activity Assay
2.10. In Vivo Studies
2.11. Immunohistochemistry (IHC) Staining
2.12. Statistics
3. Results
3.1. BCL2 Expression Increased in Enz-Resistant Prostate Cancer (PCa) Cells
3.2. BCL2 Targeting by ABT263 Impedes Cell Growth by Enhancing Enz Potency in Both Enz-Sensitive and Enz-Resistant PCa Cells
3.3. ABT263 Mechanistically Increases Enz Sensitivity by Enhancing Proteasome-Dependent Degradation of AR and ARv7
3.4. ABT263 Mechanistically Increases AR and ARv7 Degradation by Inducing Cellular ROS Level
3.5. ABT263 Increases Enz Sensitivity and AR/ARv7 Degradation via Inhibiting USP26 Activity
3.6. Preclinical Study Using in Vivo Mouse Model to Demonstrate ABT263 Can Increase Enz Sensitivity in Enz-Resistant PCa Cells and Better Suppress of PCa Progression
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Xu, H.; Sun, Y.; Huang, C.-P.; You, B.; Ye, D.; Chang, C. Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation. Cancers 2020, 12, 831. https://doi.org/10.3390/cancers12040831
Xu H, Sun Y, Huang C-P, You B, Ye D, Chang C. Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation. Cancers. 2020; 12(4):831. https://doi.org/10.3390/cancers12040831
Chicago/Turabian StyleXu, Hua, Yin Sun, Chi-Ping Huang, Bosen You, Dingwei Ye, and Chawnshang Chang. 2020. "Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation" Cancers 12, no. 4: 831. https://doi.org/10.3390/cancers12040831
APA StyleXu, H., Sun, Y., Huang, C.-P., You, B., Ye, D., & Chang, C. (2020). Preclinical Study Using ABT263 to Increase Enzalutamide Sensitivity to Suppress Prostate Cancer Progression Via Targeting BCL2/ROS/USP26 Axis Through Altering ARv7 Protein Degradation. Cancers, 12(4), 831. https://doi.org/10.3390/cancers12040831