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Página principal > Artículos > Artículos publicados > Targeting protein kinase CK2 : |
Fecha: | 2017 |
Resumen: | 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. |
Ayudas: | Ministerio de Economía y Competitividad SAF2014-52332-R |
Derechos: | 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. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Glioma ; Preclinical brain tumour ; GBM therapeutic target ; CK2 inhibitors ; CX-4945 ; Metronomic therapy ; Immune system |
Publicado en: | Pharmaceuticals, Vol. 10 Núm. 1 (2017) , p. art 24, ISSN 1424-8247 |
Article 18 p, 1.8 MB |
Material suplementari 8 p, 888.2 KB |