Interleukin-10 plasmid DNA inhibits subcutaneous tumor growth of Colon 26 adenocarcinoma in mice.
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.
Kokura
Satoshi
S
Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. s-kokura@mpd.biglobe.ne.jp
Yoshida
Norimasa
N
Ishikawa
Takeshi
T
Higashihara
Hiroshi
H
Sakamoto
Naoyuki
N
Takagi
Tomohisa
T
Uchiyama
Kazuhiko
K
Naito
Yuji
Y
Mazda
Osam
O
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D004247:DNA / Q000378:metabolism; D015316:Genetic Therapy; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000032:analysis; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010957:Plasmids; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000517:prevention & control*; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051020:bcl-X Protein / Q000032:analysis
C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D000077022:Survivin; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D016753:Interleukin-10; D004247:DNA