Sanwu Baisan decoction (三物白散) inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis

  • Yiqian JIANG ,
  • Xibin ZHOU ,
  • Wenyuan PU ,
  • Chunxiang ZHOU
Expand
  • 1 Department of Febrile Disease, Basic Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046, China
    2 Department of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, China

Received date: 2022-02-18

  Accepted date: 2022-05-25

  Online published: 2023-02-14

Supported by

National Natural Science Foundation-funded Project: the Biological Mechanism of Lingguizhugan Decoction Treating Alzheimer's Disease via Regulating Brain Lymphatic Drainage System(82074504);Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine);Natural Science Foundation of the Jiangsu Higher Education Institutions-funded Project: to Explore the Mechanism of Sanwubai San Regulating Gut Microbiota Against Colorectal Cancer By IL-23/ΓδT17/IL-17 Axis(19KJB360003)

Abstract

OBJECTIVE: To uncover the anti-tumor effects and potential mechanism of Sanwu Baisan Decoction (三物白散, SWB) in treatment of colorectal cancer (CRC) in mice.

METHODS: Therapeutic effect was evaluated based on body weight gain, tumor volume, tumor growth inhibition rate, and histological changes and apoptosis in the tumor tissues. Anti-tumor immunity was studied by measuring plasma levels of anti-tumor cytokines, interleukin 6 (IL-6), interleukin 17 (IL-17), and interferon γ (IFN-γ). Gut morphological changes were evaluated by histological staining and tight junction proteins expressions. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Classical toll-like receptor 4 (TLR-4)/ cyclooxygenase 2 (COX-2)/ prostaglandin E2 (PGE-2) pathway was examined in colon tissue and tumor samples.

RESULTS: SWB presented high anti-tumor efficacy of CRC in mice, which manifested as decreased tumor volume and increased tumor growth inhibition rate. This anti-tumor effect of SWB was associated with elevated plasma levels of anti-tumor immune cytokines (IL-6, IL-17, and IFN-γ). Further studies showed that SWB also increases the expression of occluding and promotes the abundance of gut probiotics, Clostridium_XIVa, Enterorhabdus, and uncultured_bacterium. Moreover, results suggested that the anti-tumor effects of SWB might associate with inducing cancer cell apoptosis and inhibiting the TLR-4/COX-2/PGE-2 pathway in both colon tissue and tumor samples.

CONCLUSION: SWB shows strong anti-tumor efficiency in mice with colorectal carcinoma, possibly through promoting the secretion of anti-tumor immune cytokines, inducing cancer apoptosis, maintaining the gut microbiota, and inhibiting tumorigenesis by inhibiting the TLR-4/COX-2/PGE-2 pathway.

Cite this article

Yiqian JIANG , Xibin ZHOU , Wenyuan PU , Chunxiang ZHOU . Sanwu Baisan decoction (三物白散) inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis[J]. Journal of Traditional Chinese Medicine, 2023 , 43(3) : 466 -473 . DOI: 10.19852/j.cnki.jtcm.20230214.001

References

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018; 60: 277-300.
[2] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
[3] Rafiemanesh H, Ghoncheh M, Sepehri Z, et al. Incidence and mortality of colorectal cancer and relationships with the human development index across the world. Asian Pac J Cancer Prev 2016; 17: 2465-73.
[4] Bultman J. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutr Food Res 2017; 61: 10.1002/mnfr.201500902.
[5] Cheng Y, Ling Z, Li L. The intestinal microbiota and colorectal cancer. Front Immunol 2020; 11: 615056.
[6] Chen J, Zhang H. Gut microbiota and colorectal cancer the interrelations and mechanisms. Shanghai Medi Pharm 2016; 37: 9-11.
[7] Zheng Z, Liu Z. Paneth cells: the hub for sensing and regulating intestinal flora. Sci China Life Sci 2016; 59: 463-67.
[8] Wang CY, Ding HZ, Tang X, Li ZG. Comparative analysis of immune function, hemorheological alterations and prognosis in colorectal cancer patients with different Traditional Chinese Medicine syndromes. Cancer Biomark 2017; 21: 701-10.
[9] Liang JQ, Wong SH, Szeto CH, et al. Fecal microbial DNA markers serve for screening colorectal neoplasm in asymptomatic subjects. Gastroenterol Hepatol 2020; 36: 1035-43.
[10] Huang P, Liu Y. A reasonable diet promotes balance of intestinal microbiota: prevention of precolorectal cancer. BioMed Res Int 2019: 3405278.
[11] Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One 2009; 4: e6026.
[12] Elrakaiby M, Dutilh BE, Rizkallah MR, et al. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics. OMICS 2014; 18: 402-14.
[13] Perez‐Chanona E, Jobin C. From promotion to management: the wide impact of bacteria on cancer and its treatment. BioEssays 2014; 36: 658-64..
[14] Zhao H, He M, Zhang M, et al. Colorectal cancer, gut microbiota and Traditional Chinese Medicine: a systematic review. Am J Chin Med 2021; 49: 805-28.
[15] Zhang D, Wang K, Zheng J, et al. Comparative efficacy and safety of Chinese herbal injections combined with transcatheter hepatic arterial chemoembolization in treatment of liver cancer: a bayesian network Meta-analysis. J Tradit Chin Med 2020; 40: 5-25.
[16] Zhang J, Zhan Z, Wu J, et al. Relationship between EGF, TGFA, and EGFR gene polymorphisms and Traditional Chinese Medicine Zheng in gastric cancer. Evid Based Complement Alternat Med; 2013: 731071.
[17] Wang L, Zhou GB, Liu P, et al. Dissection of mechanisms of chinese medicinal formula realgar-indigo naturalis as an effective treatment for promyelocytic leukemia. Proc Natl Acad Sci USA 2008; 105: 4826-31.
[18] Lu J. Protectiveeffect of eliminating phlegm and fluid-purging exercise on lipopolysaccharide induced acute lung injury in rats. Zhong Hua Zhong Yi Yao Xue Kan 2008; 26: 1347-49.
[19] Li QH, Zhu Y, Zou JJ. Effect of 三物白散 on apoptosis and survivin expression of gastric cancer cell line SGC-7901. Zhong Guo Zhong Yi Yao Xin Xi Za Zhi 2012; 19: 35-7.
[20] Wang M. Liu HY, Zhou CX. Normal phase immunity-regulating effect of sanwubai powder in treating tumor. Nanjing Zhong Yi Yao Da Xue Xue Bao 2006; 22: 83-5.
[21] Xu L. Experimental research on chemical prevention effects of modified sanwubai powder. Materia Med Res 2005; 6: 1226-7.
[22] Lin X, Xu WJ, Shao M, et al. Shenling baizhu san supresses colitis associated colorectal cancer through inhibition of epithelial-mesenchymal transition and myeloid-derived suppressor infiltration. BMC Complement Altern Med 2015; 15: 126.
[23] Deng W, Sui H, Wang QL, et al. A Chinese herbal formula, Yi-Qi-Fu-Sheng, inhibits migration/invasion of colorectal cancer by down-regulating MMP-2/9 via inhibiting the activation of ERK/MAPK signaling pathways. BMC Complement Altern Med 2013; 13: 65.
[24] Sivan A, Corrales L, Hubert N, et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 2015; 350: 1084-9.
[25] Zhu H, He YS, Ma J, et al. The dual roles of ginsenosides in improving the anti-tumor efficiency of cyclophosphamide in mammary carcinoma mice. J Ethnopharmacol 2020; 265: 113271.
[26] Foo JB, Yazan LS, Tor YS, et al. Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway. J Ethnopharmacol 2015; 166: 270-8.
[27] Kholoud A, Iratni R, Takahashi T, et al. Inhibitory effects of salinomycin on cell survival, colony growth, migration, and invasion of human non-small cell lung cancer A549 and LNM35: involvement of NAG-1. PLoS One 2013; 8: e66931.
[28] Greenhough E, Smartt HJ, Moore AE, et al. The COX-2/PGE 2 pathway: key roles in the hallmarks of cancer and adaptation to the. Carcinogenesis 2009; 30: 377-86.
[29] Fukata M, Chen A, Klepper A, et al. Cox-2 is regulated by toll-like receptor-4 (TLR4) signaling and is important for proliferation and apoptosis in response to intestinal mucosal injury. J Gastroenterology 2006; 131: 862-77.
Outlines

/