Chemopreventive effects of berberine on intestinal tumor development in Apcmin/+mice

BMC Gastroenterology

Research Article

Tianhui Hu¹  Bangmao Wang²  Hui Zhang²  Shuli Song²  Yang Jing²  Hailong Cao²  Rui Qu²  Boli Yang²  Yujie Zhang³  Fang Yan⁴ 

[1] Cancer Research Center, Xiamen University Medical College, 361005, Xiamen, China;Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, 154 Anshan Road in Heping District, 300052, Tianjin, China;Department of Pathology, General Hospital, Tianjin Medical University, 300052, Tianjin, China;Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 37232, Nashville, TN, USA;

关键词: Berberine;    Intestinal tumor;    Proliferation;    Apoptosis;    Wnt;    Epidermal growth factor receptor;    Apc;   

DOI  :  10.1186/1471-230X-13-163

 received in 2013-04-22, accepted in 2013-11-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundBerberine, an isoquinoline alkaloid, has shown inhibitory effects on growth of several tumor cell lines in vitro. The aim of this study was to investigate chemopreventive effects of berberine on intestinal tumor development in Apcmin/+ mice.MethodsFour-week old Apcmin/+ mice were treated with 0.05% or 0.1% berberine in drinking water for twelve weeks. The number and the size of tumors were measured to evaluate intestinal tumor development. Tissue sections were prepared for PCNA and Ki-67 immunostaining to detect cell proliferation, and TUNEL assay and cleaved caspase-3 immunostaining for apoptosis. Western blot analysis and immunostaining were performed to detect the activation of Wnt and epidermal growth factor receptor (EGFR) signaling pathways and COX-2 expression in the intestinal tumor cells. The prostaglandin E2 level in the small intestine was detected using ELISA.ResultsCompared with untreated Apcmin/+ mice, the total numbers of tumors in the small intestine and the colon were reduced by 39.6% and 62.5% in 0.05% and 0.1% berberine-treated mice, respectively. The numbers of tumors in proximal, middle, and distal segments of the small intestine in 0.1% berberine-treated mice were significantly reduced by 53.7%, 55.3%, and 76.5% respectively. Berberine treatment also decreased the numbers of all sizes of tumors (>2 mm, 1–2 mm, and <1 mm) in the small intestine. Berberine suppressed tumor cell proliferation and increased apoptosis. Furthermore, berberine decreased the activation levels of Wnt and EGFR signaling pathways, and down-regulated COX-2 expression in intestinal tumor cells and prostaglandin E2 production in the small intestine.ConclusionsBerberine inhibits intestinal tumor development, which is correlated with its activity to suppress tumor cell proliferation and increase apoptosis in Apcmin/+ mice. Down-regulation of Wnt and EGFR signaling pathways and COX-2 expression by berberine may be involved in its anti-tumorigenic effects.

【 授权许可】

Unknown   
© Cao et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.