Type I interferons in the treatment of pancreatic cancer: mechanisms of action and role of related receptors.
Ann Surg
; 246(2): 259-68, 2007 Aug.
Article
em En
| MEDLINE
| ID: mdl-17667505
ABSTRACT
OBJECTIVE:
We evaluated the role of type I interferons (IFNs) and IFN receptors in the regulation of cell growth in 3 human pancreatic adenocarcinoma cell lines (BxPC-3, MiaPaCa-2, and Panc-1).BACKGROUND:
Chemotherapy and radiotherapy have a marginal role in the management of pancreatic adenocarcinoma. The addition of IFN-alpha showed promising results in early clinical trials.METHODS:
Cell proliferation and apoptosis were evaluated by DNA measurement and DNA fragmentation, respectively. Type I IFN receptor (IFNAR-1 and IFNAR-2 subunits) was determined by quantitative RT-PCR and immunocytochemistry. Cell cycle distribution was evaluated by propidium iodide staining and flow-cytometric analysis.RESULTS:
The incubation with IFN-beta for 6 days showed a potent inhibitory effect on the proliferation of BxPC-3 (IC(50), 14 IU/mL) and MiaPaCa-2 (IC(50), 64 IU/mL). The inhibitory effect of IFN-beta was stronger than IFN-alpha in all 3 cell lines and mainly modulated by the stimulation of apoptosis, although cell cycle arrest was induced as well. The expression of the type I IFN receptors was significantly higher in BxPC-3 (the most sensitive cell line to IFN) and mainly localized on the membrane, whereas in Panc-1 (the most resistant cell line) about 60% to 70% of cells were negative for IFNAR-2c with a mainly cytoplasmic staining for IFNAR-2c.CONCLUSION:
The antitumor activity of IFN-beta is more potent than IFN-alpha in pancreatic cancer cell lines through the induction of apoptosis. Further studies should investigate in vivo whether the intensity and distribution of IFNAR-1 and IFNAR-2c may predict the response to therapy with IFN-alpha and IFN-beta in pancreatic cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
RNA Mensageiro
/
Adenocarcinoma
/
Interferon Tipo I
/
Regulação Neoplásica da Expressão Gênica
/
Receptor de Interferon alfa e beta
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Ann Surg
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Holanda