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Journal of Integrative Medicine ›› 2021, Vol. 19 ›› Issue (1): 56-65.doi: https://doi.org/10.1016/j.joim.2020.11.001

• Original Experimental Research • Previous Articles     Next Articles

Evodiamine inhibits high-fat diet-induced colitis-associated cancer in mice through regulating the gut microbiota

Li-qing Zhua,b,c, Li Zhangd, Jia Zhange, Guo-lin Changc, Gang Liuf, Dan-dan Yuc, Xiao-min Yuc, Mi-sheng Zhaoe, Bin Yea,b   

  1. a. Department of Pathogenic Biology, Chongqing Medical University, Chongqing 400016, China
    b. Research Center for Molecular Medicine and Tumor, Chongqing Medical University, Chongqing 400016, China
    c. Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325023, Zhejiang Province, China
    d. Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China
    e. Department of Clinical Laboratory, Wenzhou People’s Hospital, Wenzhou 325023, Zhejiang Province, China
    f. Department of Emergency, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China
  • Online:2021-01-12 Published:2020-11-25
  • Contact: Mi-sheng Zhao zhaomisheng@126.com;Bin Ye yebin@cqmu.edu.cn

Objective 

High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention.

Methods

Gut microbiota, serum D-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum D-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2′-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays.

Results

In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of BifidobacteriumCampylobacter and Lactobacillus were decreased. Serum endotoxin and D-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while BifidobacteriumCampylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and D-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group.

Conclusion

EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

Key words: Evodiamine, Gut microbiota, Colitis-associated cancer, Signal transducer and activator of transcription 3

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