Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon26 adenocarcinoma in mice

The transcription factor NF-kappaB is constitutively activated in many human cancers, and induces the expression of multiple proteins including antiapoptotic proteins. Recent papers indicate that NF-kappaB activation is inhibited by interleukin (IL)-10. In this study, we investigated the effect of IL-10 plasmid DNA on colon cancer in mice. In vitro study: Colon26 murine colon adenocarcinoma cells were either treated or untreated with IL-10 for 60 min. The cells were subsequently stimulated with TNF-alpha. In vivo study: to induce a high level of IL-10 in plasma, we transferred the naked plasmid vectors encoding the mouse IL-10 gene into the liver via the intravenous route. To establish tumors, we injected Colon26 cells into BALB/c mice subcutaneously. In vitro study: a 24-h incubation with TNF-alpha did not affect cell viabilities; however, pretreatment with IL-10 significantly enhanced the level of apoptosis induced by TNF-alpha. Pretreating Colon26 cells with IL-10 significantly attenuated the TNF-alpha-induced NF-kappaB activation. In vivo study: IL-10 plasmid controlled the growth of subcutaneous tumors. In subcutaneous tumor, NF-kappaB was activated in response to tumor growth. IL-10 plasmid markedly inhibited this activation of NF-kappaB in subcutaneous tumor. IL-10 plasmid induced cancer cell apoptosis linked to the down-regulation of antiapoptotic proteins, and the activation of caspase-3. These results demonstrate that IL-10 plasmid may constitute a new strategy for treating cancer growth. (C) 2004 Elsevier Ireland Ltd. All rights reserved.