Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon 26 adenocarcinoma in mice.

Abstract

The transcription factor NF-kappa B is constitutively activated in many human cancers, and induces the expression of multiple proteins including antiapoptotic proteins. Recent papers indicate that NF-kappa B 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: Colon 26 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 Colon 26 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 Colon 26 cells with IL-10 significantly attenuated the TNF-alpha-induced NF-kappa B activation. In vivo study: IL-10 plasmid controlled the growth of subcutaneous tumors. In subcutaneous tumor, NF-kappa B was activated in response to tumor growth. IL-10 plasmid markedly inhibited this activation of NF-kappa B 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.

• Authors: Satoshi Kokura, Norimasa Yoshida, Takeshi Ishikawa, Hiroshi Higashihara, Naoyuki Sakamoto, Tomohisa Takagi, Kazuhiko Uchiyama, Yuji Naito, Osam Mazda, Takeshi Okanoue, Toshikazu Yoshikawa
• Journal: Cancer letters (Cancer Lett) Vol. 218 Issue 2 Pg. 171-9 (Feb 10 2005) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 15670894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Birc5 protein, mouse
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Repressor Proteins
• Survivin
• Tumor Necrosis Factor-alpha
• bcl-X Protein
• Interleukin-10
• DNA

Topics

• Adenocarcinoma (pathology, therapy)
• Animals
• Apoptosis (drug effects)
• Colonic Neoplasms (pathology, therapy)
• DNA (metabolism)
• Genetic Therapy
• In Situ Nick-End Labeling
• Inhibitor of Apoptosis Proteins
• Interleukin-10 (blood, genetics)
• Male
• Mice
• Mice, Inbred BALB C
• Microtubule-Associated Proteins (analysis)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Plasmids
• Proto-Oncogene Proteins c-bcl-2 (analysis)
• Repressor Proteins
• Skin Neoplasms (prevention & control)
• Survivin
• Tumor Necrosis Factor-alpha (pharmacology)
• bcl-X Protein (analysis)