Enhancement of susceptibility to Fas-mediated apoptosis in oral squamous cell carcinoma cells by phosphatidylinositol 3-kinase inhibitor.
Oral Oncol
; 42(7): 745-52, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16527514
ABSTRACT
In general, oral squamous cell carcinoma (OSCC) cells are relatively resistant to Fas-mediated apoptosis during in vitro culture. Here, we studied the role of survival/apoptosis associated phosphatidylinositol 3-kinase (PI 3-K)/Akt in this process. We found that both PI 3-K inhibitors, wortmannin and LY294002, markedly suppressed the phosphorylation of Akt and accelerated Fas-mediated apoptosis in OSCC cells. It was found that caspase-3 and -8 inhibitors reduced the accelerative effect of PI 3-K inhibitor on Fas-mediated apoptosis in OSCC cells, but not caspase-9 inhibitor. Although PI 3-K inhibitors did not affect the Fas expression of OSCC cells, cellular FLICE-inhibitory protein (c-FLIP) levels were markedly reduced by PI 3-K inhibitor treatment. Moreover, antisense oligonucleotide to c-FLIP confirmed that the down-regulation of c-FLIP enhanced the sensitization to Fas-mediated apoptosis in OSCC cells. These results suggest that PI 3-K/Akt signaling pathway may, in part, regulate Fas-mediated apoptosis in OSCC cells through c-FLIP expression.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Bucais
/
Carcinoma de Células Escamosas
/
Apoptose
/
Receptor fas
/
Inibidores Enzimáticos
/
Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Humans
Idioma:
En
Revista:
Oral Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão