Kras gene mutation as a predictor of cancer cell responsiveness to metformin.
Mol Med Rep
; 8(3): 763-8, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23877793
ABSTRACT
An increasing number of studies support the use of metformin, a common antidiabetic drug, as a novel anticancer therapeutic. However, its mechanism of action has yet to be identified. In the current study, metformin was observed to effectively inhibit the growth of the K-ras mutant but not wild-type tumors in vivo. The antitumor effects of metformin were mediated by the induction of apoptosis and inhibition of proliferation in vivo. In addition, metformin induced apoptosis in the K-ras mutant tumors, A549 and PANC-1, but not in the K-ras wild-type tumor, A431, in vitro. Similarly, at lower concentrations, metformin inhibited cell proliferation in the K-ras mutant, but not in the K-ras wild-type tumor cells in vitro. These observations indicate that tumors with K-ras mutations are sensitive to metformin therapy. In addition, metformin significantly arrested K-ras mutant and wild-type tumor cells in G1 phase in vitro and metformin downregulated two important downstream effectors of the Ras signaling pathway in K-ras mutant tumors. Metformin was concluded to function as a potential K-ras-targeting agent that has potential for cancer therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Pulmonar de Células não Pequenas
/
Proteínas ras
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Neoplasias Pulmonares
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Metformina
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article