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Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation
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 viv...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136890/ https://www.ncbi.nlm.nih.gov/pubmed/37185713 http://dx.doi.org/10.3390/cimb45040189 |
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author | Wang, Dan-Yang Ohnuma, Shinobu Suzuki, Hideyuki Ishida, Masaharu Ishii, Kentaro Hirosawa, Takashi Hirashima, Tomoaki Murakami, Megumi Kobayashi, Minoru Kudoh, Katsuyoshi Haneda, Sho Musha, Hiroaki Naitoh, Takeshi Unno, Michiaki |
author_facet | Wang, Dan-Yang Ohnuma, Shinobu Suzuki, Hideyuki Ishida, Masaharu Ishii, Kentaro Hirosawa, Takashi Hirashima, Tomoaki Murakami, Megumi Kobayashi, Minoru Kudoh, Katsuyoshi Haneda, Sho Musha, Hiroaki Naitoh, Takeshi Unno, Michiaki |
author_sort | Wang, Dan-Yang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10136890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101368902023-04-28 Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation Wang, Dan-Yang Ohnuma, Shinobu Suzuki, Hideyuki Ishida, Masaharu Ishii, Kentaro Hirosawa, Takashi Hirashima, Tomoaki Murakami, Megumi Kobayashi, Minoru Kudoh, Katsuyoshi Haneda, Sho Musha, Hiroaki Naitoh, Takeshi Unno, Michiaki Curr Issues Mol Biol Article 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. MDPI 2023-04-01 /pmc/articles/PMC10136890/ /pubmed/37185713 http://dx.doi.org/10.3390/cimb45040189 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Dan-Yang Ohnuma, Shinobu Suzuki, Hideyuki Ishida, Masaharu Ishii, Kentaro Hirosawa, Takashi Hirashima, Tomoaki Murakami, Megumi Kobayashi, Minoru Kudoh, Katsuyoshi Haneda, Sho Musha, Hiroaki Naitoh, Takeshi Unno, Michiaki Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title | Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title_full | Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title_fullStr | Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title_full_unstemmed | Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title_short | Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation |
title_sort | infliximab inhibits colitis associated cancer in model mice by downregulating genes associated with mast cells and decreasing their accumulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136890/ https://www.ncbi.nlm.nih.gov/pubmed/37185713 http://dx.doi.org/10.3390/cimb45040189 |
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