Evaluation of IFN-γ effects on apoptosis and gene expression in neuroblastoma—Preclinical studies

摘要: Loss of caspase-8 expression and resistance to cytotoxic agents occurs frequently in late stage neuroblastoma (NB). Interferon-gamma (IFN-gamma) induces NB cells, sensitizing them death receptor mediated apoptosis. This study characterizes the kinetics this phenomenon examines effects IFN-gamma on global gene determine whether responses are achievable at physiologically relevant doses define biological cytokine. Here we examine 16 cell lines. A single <5-min exposure (0.5 ng/ml) induced all non-expressing lines 3/6 which already expressed high caspase-8. increase proteins was observed within h persisted for up 9 days. Furthermore, pretreatment cells increased doxorubicin-induced apoptosis nearly 3-fold. Microarray analysis used identify additional genes involved proliferation, signaling whose modulated via IFN-gamma. Altered these should further enhance responsiveness chemotherapeutics. Thus, use sensitize represents an attractive therapeutic strategy warrants investigation.