Role of the Akt/mTOR survival pathway in cisplatin resistance in ovarian cancer cells.
Biochem Biophys Res Commun
; 394(3): 600-5, 2010 Apr 09.
Article
em En
| MEDLINE
| ID: mdl-20214883
ABSTRACT
The mechanism of cisplatin resistance in cancer cells is not fully understood. Here, we show that the Akt/mTOR survival pathway plays an important role in cisplatin resistance in human ovarian cancer cells. Specifically, we found that cisplatin treatment activates the Akt/mTOR survival pathway and that inhibition of this pathway by the PI3K inhibitor LY294002 or knockdown of Akt sensitizes ovarian cancer cells to cisplatin. Furthermore, we generated cisplatin-resistant cells and found that resistant cells express a higher level of activated Akt as compared to their cisplatin sensitive counterparts. Importantly, inhibition of Akt or mTOR sensitized resistant cells to cisplatin-induced apoptosis. Taken together, our data indicate that activation of the Akt/mTOR pathway prevents cisplatin-induced apoptosis, leading to cisplatin resistance. Therefore, our study suggests that cisplatin resistance can be overcome by targeting the Akt/mTOR survival pathway in human ovarian cancer cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisplatino
/
Proteínas Serina-Treonina Quinases
/
Resistencia a Medicamentos Antineoplásicos
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteínas Proto-Oncogênicas c-akt
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article