Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Therapeutic Reagents
2.2. HNSCC Cell Lines
2.3. siRNA Depletion
2.4. Western Blot
2.5. Real-Time Impedance Assay
2.6. Colony Formation Assays
2.7. Cell Cycle Analysis
2.8. Flow Cytometry Analysis
2.9. Annexin V Assay
2.10. XTT Viability and Cell Death Assay
2.11. In Vitro Radiation
2.12. NFκB Reporter Analysis
2.13. qRT-PCR Analysis
2.14. ELISA
2.15. Statistical Analysis
3. Results
3.1. Combined Inhibition of IAPs and WEE1 Enhances the Inhibitory Effects of TNFα on Proliferation and Survival of HNSCC In Vitro
3.2. Combination Treatment Induces Cell Death through Multiple Cell Death Pathways
3.3. Depletion of WEE1 in Combination with IAP Inhibiton Also Enhances the Inhibitory Effects of TNFα on Proliferation and Survival of HNSCC In Vitro
3.4. Combination Treatment Modulates the IKK-NFκB in HNSCC Cells
3.5. Combination Treatment Sensitizes HNSCC to Radiation Treatment and Induces DNA Damage
3.6. Mutated TP53 Is a Potential Determinant of Sensitivity to Combination Therapy in HNSCC Cells
3.7. Intrinsic TNFα Production Plays a Critical Role in the Response to IAP/WEE1 Inhibition in the Highly Sensitive Cell Line UMSCC-1
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Toni, T.; Viswanathan, R.; Robbins, Y.; Gunti, S.; Yang, X.; Huynh, A.; Cheng, H.; Sowers, A.L.; Mitchell, J.B.; Allen, C.T.; et al. Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma. Cancers 2023, 15, 1029. https://doi.org/10.3390/cancers15041029
Toni T, Viswanathan R, Robbins Y, Gunti S, Yang X, Huynh A, Cheng H, Sowers AL, Mitchell JB, Allen CT, et al. Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma. Cancers. 2023; 15(4):1029. https://doi.org/10.3390/cancers15041029
Chicago/Turabian StyleToni, Tiffany, Ramya Viswanathan, Yvette Robbins, Sreenivasulu Gunti, Xinping Yang, Angel Huynh, Hui Cheng, Anastasia L. Sowers, James B. Mitchell, Clint T. Allen, and et al. 2023. "Combined Inhibition of IAPs and WEE1 Enhances TNFα- and Radiation-Induced Cell Death in Head and Neck Squamous Carcinoma" Cancers 15, no. 4: 1029. https://doi.org/10.3390/cancers15041029