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In-vitro and in-vivo anti-breast cancer activity of synergistic effect of berberine and exercise through promoting the apoptosis and immunomodulatory effects.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-07-21 , DOI: 10.1016/j.intimp.2020.106787
Wenyu Ma 1 , Yaru Zhang 1 , Min Yu 1 , Bin Wang 1 , Shiyu Xu 1 , Jian Zhang 1 , Xuegang Li 2 , Xiaoli Ye 1
Affiliation  

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.



中文翻译:

体外和体内抗乳腺癌活性小ber碱的协同作用与运动通过促进细胞凋亡和免疫调节作用有关。

目的

乳腺癌是女性癌症死亡的最常见原因。黄连的主要生物碱小ber碱(BBR)具有抗癌活性。运动是一种针对癌症的新型免疫疗法。但是,尚不清楚运动与BBR联合治疗是否对乳腺癌有影响,运动是否具有协同抗癌作用。因此,假设运动可以通过免疫方式发挥抗癌作用。

方法

在小鼠中研究了运动和体内BBR的抗肿瘤作用。进行MTT法,hoechst染色和细胞形态学研究以确定运动和BBR在体外对乳腺癌的协同作用。同时,采用Western blotting,肠道微生物和SCFA检测,Q-PCR等方法研究了其抗癌分子机制。

结果

研究发现,运动和BBR共同治疗可显着减慢4T1荷瘤小鼠的乳腺癌进展(p <0.01)。与TC组相比,BBR和运动联合组的NK细胞浸润增加(p <0.01),免疫因子和细胞因子的表达也受到调节​​。同时,协同作用显着提高了短链脂肪酸(SCFA)的水平。SCFA可以促进4T1细胞的凋亡并在体外改变炎症因子。在体外实验中,肿瘤组织中bcl-2和XIAP的表达降低,而Fas,Fadd,Bid,Cyto-C和Caspase-3 / 8/9的表达也增加(p <0.05)。

结论

这些结果表明,运动与BBR的协同治疗可以改善免疫系统,调节肠道微生物代谢产物(SCFA),激活线粒体凋亡途径和Fas死亡受体凋亡途径,从而发挥抗癌作用。这可能提供治疗乳腺癌的新方法。

更新日期:2020-07-21
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