Successful Partnerships: Exploring the Potential of Immunogenic Signals Triggered by TMZ, CX-4945, and Combined Treatment in GL261 Glioblastoma Cells

Autor: Victor J. Yuste, Laura Martínez-Escardó, Ana Paula Candiota, Lucia Villamañan, Carles Arús
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Preclinical glioblastoma
temozolomide
Pharmacology
calreticulin
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Adenosine Triphosphate
Immunogenic signals
Antineoplastic Combined Chemotherapy Protocols
Cytotoxic T cell
Casein Kinase II
lcsh:QH301-705.5
Spectroscopy
Cancer immune cycle
0303 health sciences
biology
Brain Neoplasms
immunogenic signals
General Medicine
Combined Modality Therapy
3. Good health
Computer Science Applications
Treatment Outcome
030220 oncology & carcinogenesis
Trypan blue
medicine.drug
Propidium
Signal Transduction
Cell Survival
cancer immune cycle
Catalysis
Article
Inorganic Chemistry
preclinical glioblastoma
03 medical and health sciences
In vivo
Cell Line
Tumor
medicine
Temozolomide
Humans
Viability assay
Propidium iodide
Protein kinase CK2
Physical and Theoretical Chemistry
Naphthyridines
Molecular Biology
Antineoplastic Agents
Alkylating
030304 developmental biology
Inflammation
Organic Chemistry
In vitro
ATP
chemistry
Microscopy
Fluorescence
lcsh:Biology (General)
lcsh:QD1-999
protein kinase CK2
biology.protein
Phenazines
Glioblastoma
Calreticulin
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 3453, p 3453 (2021)
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
International Journal of Molecular Sciences
Volume 22
Issue 7
ISSN: 1661-6596
1422-0067
Popis: Altres ajuts: Universitat Autònoma de Barcelona (13th PIF Call); XarTEC SALUT (2018 XARDI 00016 / IU68-013944) 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. 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. 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. 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.
Databáze: OpenAIRE
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