Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
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- Dan-Yang Wang
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Shinobu Ohnuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Hideyuki Suzuki
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Masaharu Ishida
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Kentaro Ishii
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Takashi Hirosawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Tomoaki Hirashima
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Megumi Murakami
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Minoru Kobayashi
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Katsuyoshi Kudoh
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Sho Haneda
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Hiroaki Musha
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Takeshi Naitoh
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
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- Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
抄録
<jats:p>Inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.</jats:p>
収録刊行物
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- Current Issues in Molecular Biology
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Current Issues in Molecular Biology 45 (4), 2895-2907, 2023-04-01
MDPI AG