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Synbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse model

dc.contributor.authorSaito, Yasufumi
dc.contributor.authorHinoi, Takao
dc.contributor.authorAdachi, Tomohiro
dc.contributor.authorMiguchi, Masashi
dc.contributor.authorNiitsu, Hiroaki
dc.contributor.authorKochi, Masatoshi
dc.contributor.authorSada, Haruki
dc.contributor.authorSotomaru, Yusuke
dc.contributor.authorSakamoto, Naoya
dc.contributor.authorSentani, Kazuhiro
dc.contributor.authorOue, Naohide
dc.contributor.authorYasui, Wataru
dc.contributor.authorTashiro, Hirotaka
dc.contributor.authorOhdan, Hideki
dc.date.accessioned2020-07-21T22:42:26Z
dc.date.available2020-07-21T22:42:26Z
dc.date.issued2019-06-26
dc.identifier.citationSaitoY, HinoiT, AdachiT, MiguchiM,NiitsuH, KochiM, et al. (2019)Synbioticssuppresscolitis-inducedtumorigenesis in a colon-specificcancermousemodel.PLoSONE 14(6):e0216393.https://doi.org/10.1371/journal.pone.021639en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/1803/10231
dc.description.abstractAlthough synbiotics may be effective in maintaining remission of inflammatory bowel disease, their anticarcinogenic effects are still debated. To address this issue, we evaluated the effects of synbiotics, probiotics, and prebiotics on tumorigenesis using a CDX2P-Cre; Apc(+/flox) mouse model harboring a colon-specific Apc knock out, which develops adenoma and adenocarcinoma of the colon. Dextran sodium sulfate (DSS)-administration promoted colonic tumor development in CDX2P-Cre; Apc(+/flox) mice, and these tumors were associated with loss of Apc heterozygosity, as confirmed by observation of well-differentiated adenocarcinomas with beta-catenin accumulation in tumor cell cytoplasm. Synbiotics-treatment suppressed dextran sodium sulfate-induced colitis in CDX2P-Cre; Apc(+/flox) mice, thereby reducing mortality, and inhibited tumorigenesis accelerated by DSS-administration. Conversely, neither probiotics nor prebiotics had any effect on inflammation and tumorigenesis. Lactobacillus casei and Bifidobacterium breve were detected in the fecal microbiota of probiotics-treated mice. Synbiotics-treatment suppressed DSS-induced expression of IL-6, STAT-3, COX-2, and TNF-alpha gene transcripts in normal colonic epithelium, indicating the possibility of suppressing tumor development. Importantly, these genes may be potential therapeutic targets in inflammation-associated colon cancer.en_US
dc.description.sponsorshipThis work was supported by JSPS KAKENHI Grant Numbers JP22390257 (2010-2012), JP25293284 (2013-2016), JP18K08694 (2018-) and by The Japanese Society of Gastroenterology Grant-in-Aid 2010. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.language.isoen_USen_US
dc.publisherPlos Oneen_US
dc.rightsCopyright:©2019Saitoet al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,provided the original author and source are credited.
dc.rights
dc.source.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216393#ack
dc.titleSynbiotics suppress colitis-induced tumorigenesis in a colon-specific cancer mouse modelen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0216393


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