In-vitro and in-vivo anti-breast cancer activity of synergistic effect of berberine and exercise through promoting the apoptosis and immunomodulatory effects

Purpose: Breast cancer is the most common reason of cancer death in women. Berberine (BBR), a main alkaloid in Coptis chinensis, exerted anti-cancer activities. Exercise is a new immunotherapy treatment against cancer. However, it is unclear whether exercise has effects on breast cancer and whether exercise has synergistic anti-cancer effect when co-treated with BBR. Thus, it is assumed that exercise might exert an anti-cancer effect through the immune way.

Method: The anti-tumor effect of exercise and BBR in vivo was studied in mice. The MTT method, hoechst staining and cell morphology were performed to determine the synergistic effect of exercise and BBR on breast cancer in vitro. At the same time, Western blotting, intestinal microbial and SCFA detection, Q-PCR and other methods were used to study the anti-cancer molecular mechanism.

Results: The study found that exercise and BBR co-treatment significantly slowed the progression of breast cancer in 4T1 tumor-bearing mice (p < 0.01). Compared with the TC group, the infiltration of NK cells increased in the combined group of BBR and exercise (p < 0.01), and the expression of immune factors and cytokines was also regulated. At the same time, the synergistic effect significantly increased the level of short chain fatty acids (SCFA). SCFA can promote apoptosis of 4T1 cells and change the inflammatory factors in vitro. The expression of bcl-2 and XIAP was reduced in tumor tissues, and the expression of Fas, Fadd, Bid, Cyto-C, and Caspase-3/8/9 was also increased in vitro experiments (p < 0.05).

Conclusions: These results indicate that the synergistic treatment of exercise and BBR can improve the immune system, regulate intestinal microbial metabolite (SCFA), activate the mitochondrial apoptosis pathway and Fas death receptor apoptosis pathway, and thus play an anticancer role. This may provide a new method for the treatment of breast cancer.

Keywords: Apoptosis; Berberine (BBR); Combination; Exercise; Immune; SCFAs.