Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization

Abstract

Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks. Primary macrophages were isolated; after berberine treatment, the change in signaling cascade was determined. The total number and size of polyps were reduced remarkably in berberine group, compared with control group. A significant decrease in protein levels of F4/80, mannose receptor (MR), and COX-2 in stroma of intestinal polyps and an increase in the level of iNOS were observed after berberine treatment. The mRNA level of MR and Arg-1 in berberine group was significantly lower than those in IL-10 or IL-4 group, while no significant difference in mRNA levels of iNOS and CXCL10 was observed. The migration and invasiveness assays in vitro showed that berberine could reduce the capability of migration and invasiveness. These findings suggest that berberine attenuates intestinal tumorigenesis by inhibiting the migration and invasion of colorectal tumor cells via regulation of macrophage polarization.

Fu-Zheng-Jie-Du Ointment Enhances the Therapeutic Efficacy of 5-fluoropyrimidine by Inhibiting TIE2-expressing Monocyte/macrophage-mediated Angiogenesis in a Mouse Gastric Cancer Model

“…The anti-tumor effect of herbs used in traditional Chinese medicine (TCM) is mediated through various mechanisms, including modulation of the tumor microenvironment (TME) [26]. The herbs used in TCM are also reported to regulate TAMs [27][28][29]. However, there are limited studies on the effect of TCM herbs on TEMs.…”

Familial adenomatous polyposis in China

“…For Chinese patients with FAP who do not consent to surgical operation, TCM is another option and has been used in the treatment of colonic disorders (86). Having developed over thousands of years, TCM is considered to be a complete system of healthcare and includes a complex herbal therapeutic component (87).…”

“…Following treatment with TCM, patients with FAP have exhibited long-term survival and reduced colorectal symptoms, which provides evidence for the use of Chinese herbal medicine in the successful prevention and treatment of FAP (83,84). Researchers in China are attempting to study the active ingredients of traditional herbal therapeutics and elucidate their mechanism of action (86,88). However, further randomized controlled trials on TCM are required.…”

Immune Microenvironment: New Insight for Familial Adenomatous Polyposis

“…Present evidence has shown that TAM especially M2 macrophages are involved in the development and progression of FAP. Accompanied with the reduction of M2 macrophage polarization, the total number and size of polyps are reduced correspondingly in a FAP mice model ( 44 ). The same phenomenon has also been verified in other studies ( 45 , 46 ).…”