Back to Search Start Over

Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation

Authors :
Dan-Yang Wang
Shinobu Ohnuma
Hideyuki Suzuki
Masaharu Ishida
Kentaro Ishii
Takashi Hirosawa
Tomoaki Hirashima
Megumi Murakami
Minoru Kobayashi
Katsuyoshi Kudoh
Sho Haneda
Hiroaki Musha
Takeshi Naitoh
Michiaki Unno
Source :
Current Issues in Molecular Biology, Vol 45, Iss 4, Pp 2895-2907 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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.

Details

Language :
English
ISSN :
14673045 and 14673037
Volume :
45
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Current Issues in Molecular Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.2e2accfa2b0434380dec5347ea7f766
Document Type :
article
Full Text :
https://doi.org/10.3390/cimb45040189