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01-12-2014 | Original Article

The secondary bile acid, deoxycholate accelerates intestinal adenoma–adenocarcinoma sequence in Apc ^min/+ mice through enhancing Wnt signaling

Authors: Hailong Cao, Shenhui Luo, Mengque Xu, Yujie Zhang, Shuli Song, Shan Wang, Xinyue Kong, Nana He, Xiaocang Cao, Fang Yan, Bangmao Wang

Published in: Familial Cancer | Issue 4/2014

Abstract

Colorectal cancer is one of the leading causes of cancer deaths. It correlates to a high fat diet, which causes an increase of the secondary bile acids including deoxycholate (DOC) in the intestine. We aimed to determine the effects of DOC on intestinal carcinogenesis in Apc ^min/+ mice, a model of spontaneous intestinal adenomas. Four-week old Apc ^min/+ mice were treated with 0.2 % DOC in drinking water for 12 weeks. The number and size of tumors were measured, and tissue sections were prepared for the evaluation of intestinal carcinogenesis, cell proliferation, and apoptosis. The activation of Wnt signaling was detected in the intestinal tumor cells of the Apc ^min/+ mice, and also in the human colon samples. DOC increased the number of intestine tumors by 165.1 % compared with that in untreated Apc ^min/+ mice mainly in the middle and distal segments of the small intestine and colon. The numbers of all sizes of tumors in the small intestine were increased. Intestinal carcinogenesis was confirmed in 75 % mice in DOC treated-Apc ^min/+ mice compared with 0 % in untreated mice. This was accompanied by promoting tumor cell proliferation and decreasing apoptosis, and increasing the percentage of β-catenin positive cells and its nuclear expression in intestinal tumor cells of Apc ^min/+ mice, and also up-regulating the expression of cyclin D1. In addition, the activation of Wnt signaling also played in modulating human colon carcinogenesis. Our studies suggest that DOC enhances the multiplicity of intestinal tumor, and accelerates intestinal adenoma–adenocarcinoma sequence in Apc ^min/+ mice mediated by stimulating tumor cell proliferation and decreasing apoptosis through enhancing Wnt signaling.

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Title: The secondary bile acid, deoxycholate accelerates intestinal adenoma–adenocarcinoma sequence in Apc min/+ mice through enhancing Wnt signaling
Authors: Hailong Cao
Shenhui Luo
Mengque Xu
Yujie Zhang
Shuli Song
Shan Wang
Xinyue Kong
Nana He
Xiaocang Cao
Fang Yan
Bangmao Wang
Publication date: 01-12-2014
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 4/2014
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-014-9742-3

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