Scopus: 5 cites, Web of Science: 5 cites,
Targeting protein kinase CK2 : evaluationg CX-4945 potential for GL261 glioblastoma therapy in immunocompetent mice
Ferrer-Font, Laura (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Villamañán de Santiago, Lucía (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Arias-Ramos, Nuria (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Vilardell Vilà, Jordi (Università degli studi di Padova. Dipartimento di Scienze Biomediche)
Plana i Coll, Maria (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Ruzzene, Maria (Università degli studi di Padova. Dipartimento di Scienze Biomediche)
Pinna, Lorenzo A. (Università degli studi di Padova. Dipartimento di Scienze Biomediche)
Itarte, Emili (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Arús i Caraltó, Carles (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)
Candiota Silveira, Ana Paula (Universitat Autònoma de Barcelona. Departament de Bioquímica i Biologia Molecular)

Data: 2017
Resum: Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129) phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0. 05) was found with combined CX-4945 and TMZ metronomic treatment (54. 7 ± 11. 9 days, n = 6) when compared to individual metronomic treatments (CX-4945: 24. 5 ± 2. 0 and TMZ: 38. 7 ± 2. 7, n = 6) and controls (22. 5 ± 1. 2, n = 6). Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response.
Nota: Número d'acord de subvenció MINECO/SAF2014-52332-R
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Glioma ; Preclinical brain tumour ; GBM therapeutic target ; CK2 inhibitors ; CX-4945 ; Metronomic therapy ; Immune system
Publicat a: Pharmaceuticals, Vol. 10 Núm. 1 (2017) , p. art 24, ISSN 1424-8247

DOI: 10.3390/ph10010024
PMID: 28208677


Article
18 p, 1.8 MB

Material suplementari
8 p, 888.2 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2017-02-14, darrera modificació el 2017-10-23



   Favorit i Compartir