Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy.
Clin Exp Dermatol
; 38(4): 421-3, 2013 Jun.
Article
em En
| MEDLINE
| ID: mdl-23530461
ABSTRACT
Early-stage cutaneous squamous cell carcinoma (cSCC) has a favourable prognosis. Metastatic disease is probably associated with chemoresistance mediated through the activation of pro-survival phosphatidylinositol 3-kinase/AKT signalling. Inhibition of activated AKT partially increases chemosensitivity but induces autophagy, the principal lysosomal mechanism for the bulk degradation and recycling of proteins and damaged organelles. The aim of the current study was to test the hypothesis that combined inhibition of AKT signalling and autophagy by the lysosomal inhibitor chloroquine increases the susceptibility to docetaxel-induced apoptosis of cSCC cells isolated from a lymph-node metastasis. Combined AKT inhibition and chloroquine treatment of MET 4 cSCC cells resulted in significantly enhanced inhibition of cell viability and apoptosis induced by clinically achievable concentrations of docetaxel (P < 0.001). Inhibition of both autophagy and AKT thus represents an effective and viable therapeutic strategy to increase the cytotoxicity of docetaxel for the treatment of advanced cSCC.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
/
Autofagia
/
Carcinoma de Células Escamosas
/
Taxoides
/
Inibidores Enzimáticos
/
Inibidores de Fosfoinositídeo-3 Quinase
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article