Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-ß/IκBα/NFκB axis.
Oncotarget
; 7(45): 73032-73044, 2016 Nov 08.
Article
em En
| MEDLINE
| ID: mdl-27682876
ABSTRACT
Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-ß/IκBα/NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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NF-kappa B
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Carcinoma Mucoepidermoide
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Quinase I-kappa B
Limite:
Humans
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article