Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. GL261 Cell Culture
2.2. Cell Treatments
2.3. Cell Viability Assays
2.3.1. Trypan Blue Exclusion Assay
2.3.2. Flow Cytometry Analysis with Propidium Iodide
2.4. DAMPs Release/Exposure Assessment
2.4.1. Immunofluorescence for CRT Detection
2.4.2. Bioluminescent Assay for ATP Measurement
Extracellular ATP
Intracellular ATP
2.5. Statistical Analysis
3. Results
3.1. Effects over GL261 Cell Viability
3.1.1. TMZ Single Treatment
3.1.2. CX-4945 Single Treatment
3.1.3. CX-4945 and TMZ Combined Treatment
3.2. Immunogenic Cell Death Signals Triggered In Vitro under TMZ and CX-4945 Treatment Alone and in Combination
3.2.1. Calreticulin Exposure
3.2.2. Assessment of ATP Release
Cytotoxicity Assessment after Short Treatment Times: Can It Affect ATP Release?
4. Discussion
4.1. TMZ Is Not Enough: Pursuing Better Combinations/Schedules
4.2. Immunogenic Potential of Single and Combined Treatments and Possible Pitfalls While Interpreting Results
4.3. Word of Caution While Interpreting the Additive Effect of Immunogenic Signals In Vitro
4.4. In Vitro Studies Do Not Properly Mimic the In Vivo Environment
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | Range of Concentrations Assayed | Range of Treatment Time (h) |
---|---|---|
TMZ | 0.5–4 mM | 24–72 |
CX-4945 | 25–150 µM | 12–72 |
Doxorubicin | 50 µM | 24 |
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Villamañan, L.; Martínez-Escardó, L.; Arús, C.; Yuste, V.J.; Candiota, A.P. Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells. Int. J. Mol. Sci. 2021, 22, 3453. https://doi.org/10.3390/ijms22073453
Villamañan L, Martínez-Escardó L, Arús C, Yuste VJ, Candiota AP. Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells. International Journal of Molecular Sciences. 2021; 22(7):3453. https://doi.org/10.3390/ijms22073453
Chicago/Turabian StyleVillamañan, Lucía, Laura Martínez-Escardó, Carles Arús, Victor J. Yuste, and Ana P. Candiota. 2021. "Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells" International Journal of Molecular Sciences 22, no. 7: 3453. https://doi.org/10.3390/ijms22073453