The secondary bile acid, deoxycholate accelerates intestinal adenoma–adenocarcinoma sequence in Apc min/+ mice through enhancing Wnt signaling
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- 作者：Hailong Cao (1)
Shenhui Luo (1) (2)
Mengque Xu (1)
Yujie Zhang (3)
Shuli Song (1)
Shan Wang (1)
Xinyue Kong (1)
Nana He (1)
Xiaocang Cao (1)
Fang Yan (1) (4)
Bangmao Wang (1) - 关键词：Deoxycholate ; Intestinal tumor ; Apc min/+ mice ; Wnt signaling
- 刊名：Familial Cancer
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：13
- 期：4
- 页码：563-571
- 全文大小：12,685 KB
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18. Wasan HS, Novelli M, Bee J, Bodmer - 作者单位：Hailong Cao (1)
Shenhui Luo (1) (2)
Mengque Xu (1)
Yujie Zhang (3)
Shuli Song (1)
Shan Wang (1)
Xinyue Kong (1)
Nana He (1)
Xiaocang Cao (1)
Fang Yan (1) (4)
Bangmao Wang (1)
1. Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, 154 Anshan Road in Heping District, Tianjin, 300052, China
2. Department of Gastroenterology, People’s Hospital of Xiangxi Autonomous Prefecture, Ji shou City, Hunan Province, China
3. Department of Pathology, General Hospital, Tianjin Medical University, Tianjin, 300052, China
4. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA - ISSN：1573-7292
文摘
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.