Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-λ genes produced anti-tumour effects.
Br J Cancer
; 105(9): 1302-12, 2011 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-21952623
ABSTRACT
BACKGROUND:
Interferon-λs (IFN-λs) are novel cytokines with multiple functions, like IFN-α and -ß. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-λ1 or -λ2 gene (Ad/IFN-λ) with the type-35 fibre-knob structure.METHODS:
Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-λ and mechanisms of the inhibited growth were investigated.RESULTS:
Transduction with Ad/IFN-λ upregulated the expression of the class I antigens of the major histocompatibility complexes and induced the growth suppression. Increased sub-G1 populations and the cleavage of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-λ-sensitive YES-2 and T.Tn cells. The cell death was accompanied by cytoplasmic cytochrome C and increased cleaved caspase-9 and Bax expression, suggesting mitochondria-mediated apoptosis. Adenovirus/IFN-λ-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-λ-infected fibroblasts, negative for the IFN-λ receptors, induced death of YES-2 or T.Tn cells that were co-cultured. Inoculation of YES-2 cells in nude mice, when mixed with the Ad/IFN-λ-infected fibroblasts, resulted in retardation of the tumour growth. The growth suppression was not linked with upregulated CD69 expression on natural killer cells or increased numbers of CD31-positive cells.CONCLUSION:
Adenovirus/IFN-λ induced apoptosis, and fibroblast-mediated delivery of IFN-λs is a potential cancer treatment by inducing direct cell death of the target carcinoma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Esofágicas
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Terapia Genética
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Adenoviridae
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Interleucinas
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article