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Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Mar 26; Vol. 22 (7). Date of Electronic Publication: 2021 Mar 26. - Publication Year :
- 2021
-
Abstract
- Background: The relevance of the cancer immune cycle in therapy response implies that successful treatment may trigger the exposure or the release of immunogenic signals. Previous results with the preclinical GL261 glioblastoma (GB) showed that combination treatment of temozolomide (TMZ) + CX-4945 (protein kinase CK2 inhibitor) outperformed single treatments, provided an immune-friendly schedule was followed. Our purpose was to study possible immunogenic signals released in vitro by GB cells.<br />Methods: GL261 GB cells were treated with TMZ and CX-4945 at different concentrations (25 µM-4 mM) and time frames (12-72 h). Cell viability was measured with Trypan Blue and propidium iodide. Calreticulin exposure was assessed with immunofluorescence, and ATP release was measured with bioluminescence.<br />Results: TMZ showed cytostatic rather than cytotoxic effects, while CX-4945 showed remarkable cytotoxic effects already at low concentrations. Calreticulin exposure after 24 h was detected with TMZ treatment, as well as TMZ/CX-4945 low concentration combined treatment. ATP release was significantly higher with CX-4945, especially at high concentrations, as well as with TMZ/CX-4945.<br />Conclusions: combined treatment may produce the simultaneous release of two potent immunogenic signals, which can explain the outperformance over single treatments in vivo. A word of caution may be raised since in vitro conditions are not able to mimic pharmacokinetics observed in vivo fully.
- Subjects :
- Adenosine Triphosphate chemistry
Antineoplastic Agents, Alkylating administration & dosage
Calreticulin chemistry
Casein Kinase II metabolism
Cell Line, Tumor
Cell Survival
Combined Modality Therapy
Humans
Inflammation
Microscopy, Fluorescence
Propidium chemistry
Signal Transduction
Treatment Outcome
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Brain Neoplasms drug therapy
Glioblastoma drug therapy
Naphthyridines administration & dosage
Phenazines administration & dosage
Temozolomide administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33810611
- Full Text :
- https://doi.org/10.3390/ijms22073453