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

Lab Invest. 2017 Nov;97(11):1343-1353. doi: 10.1038/labinvest.2017.71. Epub 2017 Jul 31.


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 ApcMin/+ 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 ApcMin/+ 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.

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use*
  • Berberine / pharmacology
  • Berberine / therapeutic use*
  • Carcinogenesis / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colitis / drug therapy*
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / physiopathology
  • Colon / drug effects
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / prevention & control*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • RAW 264.7 Cells
  • Random Allocation


  • Adenomatous Polyposis Coli Protein
  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticarcinogenic Agents
  • adenomatous polyposis coli protein, mouse
  • Berberine
  • EGFR protein, mouse
  • ErbB Receptors