Erschienen in:
01.12.2014 | Original Article
The secondary bile acid, deoxycholate accelerates intestinal adenoma–adenocarcinoma sequence in Apc
min/+ mice through enhancing Wnt signaling
verfasst von:
Hailong Cao, Shenhui Luo, Mengque Xu, Yujie Zhang, Shuli Song, Shan Wang, Xinyue Kong, Nana He, Xiaocang Cao, Fang Yan, Bangmao Wang
Erschienen in:
Familial Cancer
|
Ausgabe 4/2014
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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.