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Abstract Title:

Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth.

Abstract Source:

Lab Invest. 2017 Jul 31. Epub 2017 Jul 31. PMID: 28759012

Abstract Author(s):

Dandan Li, Youyu Zhang, Kun Liu, Yujie Zhao, Beibei Xu, Liang Xu, Li Tan, Yuan Tian, Cunxi Li, Wenqing Zhang, Hanwei Cao, Yan-Yan Zhan, Tianhui Hu

Article Affiliation:

Dandan Li

Abstract:

The anti-inflammatory and anti-tumor effects of berberine, a traditional Chinese medicine, were separately discovered in pathological intestinal tissues. However, whether the anti-inflammatory effect of berberine contributes to its anti-tumor effect on colitis-associated colorectal cancer (CACRC) remains unknown. In the present study, we found that berberine effectively inhibited colitis-associated tumorigenesis and colonic epithelium hyperproliferation in dextran sulfate sodium (DSS)-treated Apc(Min/+) mice. A mechanistic study identified that these inhibitory effects of berberine occurred through blocking interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression in colonic macrophages. An in vitro study on cell lines identified that berberine treatment of Raw 264.7 macrophages resulted in conditioned media with fewer proliferative effects on a cell line with a heterozygous Apc mutation (Immorto-Min colonic epithelium, IMCE). EGFR-ERK signaling act downstream of berberine/pro-inflammatory cytokines axis to regulate CACRC cell proliferation. Furthermore, in vivo administration of IL-6 to DSS-treated Apc(Min/+) mice effectively weakened the inhibitory effects of berberine on tumorigenesis and EGFR-ERK signaling in colon tissues. Altogether, the results of our studies have revealed that berberine inhibits the development of CACRC by interfering with inflammatory response-driven EGFR signaling in tumor cell growth. The findings of this study support the possibility that berberine and other anti-inflammatory drugs may be beneficial in the treatment of CACRC.Laboratory Investigation advance online publication, 31 July 2017; doi:10.1038/labinvest.2017.71.

Study Type : Animal Study, In Vitro Study

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