Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Culture Conditions
2.2. Spheroid Routine Culturing and Monitoring
2.3. Hyperthermia and Irradiation Treatment
2.4. Exposure to Chemical Chaperones
2.5. Spheroid Volume Growth Delay and Spheroid Control Probability (SCP) Assays
2.6. Reverse Transcription (RT-) and Real-Time Quantitative-(q-)PCR Analyses
2.7. Western Blotting
2.8. Transcriptomics
3. Results
3.1. HT Induces Minimal Spheroid Growth Delay at Clinically Relevant Temperatures
3.2. HT Induces Sensitization of HNSCC Spheroids to Single Dose Irradiation
3.3. Global Changes in Gene Expression Profiles of HNSCC Spheroids upon HT + RT
3.4. HT Affects Main Survival and Stress Response Signaling in HNSCC Spheroids
3.5. HT Triggers Heat Shock Response (HSR) and Proteotoxic Stress in HNSCC Spheroids
3.6. HT-Induced Radiosensitization Is Adversely Affected by the Proteotoxic Stress Response
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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Spheroid Type | Readout | RT Only | HT + RT | |||
---|---|---|---|---|---|---|
42.5 °C 30 min | 42.5 °C 60 min | 44.5 °C 30 min | 46.5 °C 30 min | |||
FaDu | SCD50 (Gy) | 11.1 | 8.7 | 7.3 | 7.5 | 3.2 |
95% CI (Gy) | 10.8–11.3 | 8.4–9.1 | 7.1–7.6 | 7.3–7.8 | 3.0–3.6 | |
TER | 1.3 | 1.5 | 1.5 | 3.4 | ||
95% CI | 1.2–1.3 | 1.4–1.6 | 1.4–1.5 | 3.1–3.8 | ||
SAS | SCD50 (Gy) | 16.5 | 12.4 | 10.2 | 8.0 | 3.5 |
95% CI (Gy) | 16.2–16.8 | 12.2–12.7 | 9.9–10.5 | 7.7–8.3 | 3.3–3.9 | |
TER | 1.3 | 1.6 | 2.1 | 4.6 | ||
95% CI | 1.3–1.4 | 1.6–1.7 | 2.0–2.1 | 4.3–5.0 |
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Chen, O.; Michlíková, S.; Eckhardt, L.; Wondrak, M.; De Mendoza, A.M.; Krause, M.; McLeod, D.D.; Kunz-Schughart, L.A. Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay. Cancers 2021, 13, 3168. https://doi.org/10.3390/cancers13133168
Chen O, Michlíková S, Eckhardt L, Wondrak M, De Mendoza AM, Krause M, McLeod DD, Kunz-Schughart LA. Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay. Cancers. 2021; 13(13):3168. https://doi.org/10.3390/cancers13133168
Chicago/Turabian StyleChen, Oleg, Soňa Michlíková, Lisa Eckhardt, Marit Wondrak, Adriana M. De Mendoza, Mechthild Krause, Damian D. McLeod, and Leoni A. Kunz-Schughart. 2021. "Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay" Cancers 13, no. 13: 3168. https://doi.org/10.3390/cancers13133168