Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-genes produced anti-tumour effects

Abstract

Background: Interferon-s (IFN-s) are novel cytokines with multiple functions, like IFN-α and-Β. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-1 or-2 gene (Ad/IFN-) with the type-35 fibre-knob structure. Methods: Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-and mechanisms of the inhibited growth were investigated. Results: Transduction with Ad/IFN-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-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-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-infected fibroblasts, negative for the IFN-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-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-induced apoptosis, and fibroblast-mediated delivery of IFN-s is a potential cancer treatment by inducing direct cell death of the target carcinoma. © 2011 Cancer Research UK All rights reserved.