Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (3): 466-473.DOI: 10.19852/j.cnki.jtcm.20230214.001
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Sanwu Baisan decoction (三物白散) inhibits colorectal cancer progression in mice by remodeling gut microbiota and tumorigenesis
JIANG Yiqian1, ZHOU Xibin1,2, PU Wenyuan1(
), ZHOU Chunxiang1()
- 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:2022-02-18Accepted:2022-05-25Online:2023-06-15Published:2023-02-14 -
Contact:Dr. PU Wenyuan, Department of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, China. wenyuanpu@njucm.edu.cn. Telephone: +86-19951948590; +86-15950577300
Prof. ZHOU Chunxiang, Department of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, China. chunxiangzhou@njucm.edu.cn -
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)
Cite this article
JIANG Yiqian, ZHOU Xibin, PU Wenyuan, ZHOU Chunxiang. 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.
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Figure 1 Morphology of colon tissues in mice implanted with colon carcinoma in vivo A: representative photographs of whole intestine collected from mice treated with saline (CON, A1), SWB (5 mg/kg, A2; 10 mg/kg, A3; 50 mg/kg, A4) and DDP (0.75 mg/kg, A5). B: representative HE images of colon tissues (CON, B1), SWB (5 mg/kg, B2; 10 mg/kg, B3; 50 mg/kg, B4), DDP (0.75 mg/kg, B5) and observed changes under microscope (× 40). C: representative immunohistology images of colon tissues that were stained with Occluding from mice (CON, C1), SWB (5 mg/kg, C2; 10 mg/kg, C3; 50 mg/kg, C4), DDP (0.75 mg/kg, C5) and observed changes under microscope (× 40). D: mRNA level of COX-2 in colon samples. E: mRNA level of PGE-2 in colon samples. CON: Saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; SWB: Sanwu Baisan; DDP: cisplatin; HE: hematoxylin eosin; COX-2: cyclooxygenase 2; PGE-2: prostaglandin E2. All the treatment were lasted for 4 weeks. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05.
Figure 1 Morphology of colon tissues in mice implanted with colon carcinoma in vivo A: representative photographs of whole intestine collected from mice treated with saline (CON, A1), SWB (5 mg/kg, A2; 10 mg/kg, A3; 50 mg/kg, A4) and DDP (0.75 mg/kg, A5). B: representative HE images of colon tissues (CON, B1), SWB (5 mg/kg, B2; 10 mg/kg, B3; 50 mg/kg, B4), DDP (0.75 mg/kg, B5) and observed changes under microscope (× 40). C: representative immunohistology images of colon tissues that were stained with Occluding from mice (CON, C1), SWB (5 mg/kg, C2; 10 mg/kg, C3; 50 mg/kg, C4), DDP (0.75 mg/kg, C5) and observed changes under microscope (× 40). D: mRNA level of COX-2 in colon samples. E: mRNA level of PGE-2 in colon samples. CON: Saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; SWB: Sanwu Baisan; DDP: cisplatin; HE: hematoxylin eosin; COX-2: cyclooxygenase 2; PGE-2: prostaglandin E2. All the treatment were lasted for 4 weeks. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05.
Figure 2 SWB modulates the gut microbiota composition A1: index of Shannon. A2: Simpson. A3: Coverage of microbiome α diversity. For A1-A3, One-way ANOVA was used to calculate the significant difference among groups. B: relative abundance distribution of microbiome at the phylum level in CON, SH, and DDP group. C: the LDA scores were computed for differentially abundant taxa in the fecal microbiomes from the CON, SH, and DDP groups with P<0.05. In this LEfSe analysis, the Kruskal-Wallis test was used. D: Spearman Correlation analysis between microbiome and plasma cytokines. *P <0.05, #P <0.01. CON: Saline; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; IL-6: interleukin 6; IL-17: interleukin 17; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ. SWB: Sanwu Baisan; ANOVA: analysis of variance; LDA: linear discriminant analysis; LEfSe: linear discriminant analysis effect size; DDP: cisplatin. All the treatment were lasted for 4 weeks.
Figure 2 SWB modulates the gut microbiota composition A1: index of Shannon. A2: Simpson. A3: Coverage of microbiome α diversity. For A1-A3, One-way ANOVA was used to calculate the significant difference among groups. B: relative abundance distribution of microbiome at the phylum level in CON, SH, and DDP group. C: the LDA scores were computed for differentially abundant taxa in the fecal microbiomes from the CON, SH, and DDP groups with P<0.05. In this LEfSe analysis, the Kruskal-Wallis test was used. D: Spearman Correlation analysis between microbiome and plasma cytokines. *P <0.05, #P <0.01. CON: Saline; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; IL-6: interleukin 6; IL-17: interleukin 17; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ. SWB: Sanwu Baisan; ANOVA: analysis of variance; LDA: linear discriminant analysis; LEfSe: linear discriminant analysis effect size; DDP: cisplatin. All the treatment were lasted for 4 weeks.
Figure 3 SWB promotes cancer cell apoptosis in vivo A-B: representative images of HE staining of tumor blocks from CON (A1), SH (A2), SM (A3), SL (A4), and DDP (A5) groups (×40); B: representative images of TUNEL staining of tumor blocks from CON (B1), SH (B2), SM (B3), SL (B4), and DDP (B5) groups (×40); C: representative Western blot bands of Bax, Bcl-2, cleaved caspase 3, and cleaved caspase 9; D: quantification results of the protein expressions of Bax (D1), Bcl-2 (D2), cleaved caspase 3 (D3) and cleaved caspase 9 (D4). CON: saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; Bcl-2: B cell lymphoma 2; Bax: Bcl-2-associated X protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; SWB: Sanwu Baisan; DDP: cisplatin; HE: hematoxylin eosin; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. All the treatment were lasted for 4 weeks. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05.
Figure 3 SWB promotes cancer cell apoptosis in vivo A-B: representative images of HE staining of tumor blocks from CON (A1), SH (A2), SM (A3), SL (A4), and DDP (A5) groups (×40); B: representative images of TUNEL staining of tumor blocks from CON (B1), SH (B2), SM (B3), SL (B4), and DDP (B5) groups (×40); C: representative Western blot bands of Bax, Bcl-2, cleaved caspase 3, and cleaved caspase 9; D: quantification results of the protein expressions of Bax (D1), Bcl-2 (D2), cleaved caspase 3 (D3) and cleaved caspase 9 (D4). CON: saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; Bcl-2: B cell lymphoma 2; Bax: Bcl-2-associated X protein; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; SWB: Sanwu Baisan; DDP: cisplatin; HE: hematoxylin eosin; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. All the treatment were lasted for 4 weeks. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05.
Figure 4 SWB inhibits cancer cell invasion and proliferation in vivo A: representative bands of MMP-2, MMP-9, TLR-4, COX-2, and PGE-2; B: quantification results of protein expression of MMP-2 (B1), MMP-9 (B2), COX-2 (B3), TLR-4 (B4), and PGE-2 (B5). CON: saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; SWB: Sanwu Baisan; DDP: cisplatin; MMP-2: matrix metallopeptidase 2; MMP-9: matrix metallopeptidase 9; TLR4: toll-like receptor 4; COX-2: cyclooxygenase 2; PGE-2: prostaglandin E2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05. All the treatment were lasted for 4 weeks.
Figure 4 SWB inhibits cancer cell invasion and proliferation in vivo A: representative bands of MMP-2, MMP-9, TLR-4, COX-2, and PGE-2; B: quantification results of protein expression of MMP-2 (B1), MMP-9 (B2), COX-2 (B3), TLR-4 (B4), and PGE-2 (B5). CON: saline; SL: 5 mg/kg SWB; SM: 10 mg/kg SWB; SH: 50 mg/kg SWB; DDP: 0.75 mg/kg DDP; SWB: Sanwu Baisan; DDP: cisplatin; MMP-2: matrix metallopeptidase 2; MMP-9: matrix metallopeptidase 9; TLR4: toll-like receptor 4; COX-2: cyclooxygenase 2; PGE-2: prostaglandin E2; GAPDH: glyceraldehyde-3-phosphate dehydrogenase. Data were presented as mean ± standard deviation (n = 10). All the treated groups were compared with the CON group using the students' t-test, aP<0.05. All the treatment were lasted for 4 weeks.
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