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Open Access Research article

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

Hailong Cao1, Shuli Song1, Hui Zhang1, Yujie Zhang2, Rui Qu1, Boli Yang1, Yang Jing1, Tianhui Hu3, Fang Yan4 and Bangmao Wang1*

Author Affiliations

1 Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, 154 Anshan Road in Heping District, Tianjin 300052, China

2 Department of Pathology, General Hospital, Tianjin Medical University, Tianjin 300052, China

3 Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China

4 Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232, USA

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BMC Gastroenterology 2013, 13:163  doi:10.1186/1471-230X-13-163

Published: 27 November 2013

Abstract

Background

Berberine, 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.

Methods

Four-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.

Results

Compared 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.

Conclusions

Berberine 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.

Keywords:
Berberine; Intestinal tumor; Proliferation; Apoptosis; Wnt; Epidermal growth factor receptor; Apcmin/+ mouse