Successful partnerships : exploring the potential of immunogenic signals triggered by TMZ, CX-4945 and combined treatment in GL261 glioblastoma cells
Villamañán de Santiago, Lucía ![Identificador ORCID](/img/uab/orcid.ico)
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Martínez-Escardó, Laura ![Identificador ORCID](/img/uab/orcid.ico)
(Universitat Autònoma de Barcelona. Institut de Neurociències)
Arús i Caraltó, Carles ![Identificador ORCID](/img/uab/orcid.ico)
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Yuste, Victor José ![Identificador ORCID](/img/uab/orcid.ico)
(Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Candiota Silveira, Ana Paula ![Identificador ORCID](/img/uab/orcid.ico)
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Fecha: |
2021 |
Resumen: |
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. |
Ayudas: |
European Commission 777222 Ministerio de Sanidad y Consumo CB06/01/0010 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/XARDI-00016
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Derechos: |
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Lengua: |
Anglès |
Documento: |
Article ; recerca ; Versió publicada |
Materia: |
Preclinical glioblastoma ;
Cancer immune cycle ;
Immunogenic signals ;
Calreticulin ;
ATP ;
Protein kinase CK2 ;
Temozolomide |
Publicado en: |
International journal of molecular sciences, Vol. 22, Issue 7 (April 2021) , art. 3453, ISSN 1422-0067 |
DOI: 10.3390/ijms22073453
PMID: 33810611
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Registro creado el 2021-04-08, última modificación el 2024-05-20