Journal of Traditional Chinese Medicine ›› 2024, Vol. 44 ›› Issue (5): 896-905.DOI: 10.19852/j.cnki.jtcm.20240806.001
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Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis
ZHANG Guangshun1,2, XU Xiaonan3,4,5, XU Chuyun6, LIAO Guanghui1,2, XU Hao3,4,5, LOU Zhaohuan1,2(
), ZHANG Guangji3,4,5()
- 1 School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
2 Key Labortary of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou 310053, China
3 School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
4 Key Labortary of Blood-stasis-toxin Syndrome of Zhejiang Province, Hangzhou 310053, China
5 Traditional Chinese Medicine "Preventing Disease" Wisdom Health Project Research Center of Zhejiang, Hangzhou 310053, China
6 the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China
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Received:2023-04-21Accepted:2023-08-29Online:2024-10-15Published:2024-08-06 -
Contact:Prof. ZHANG Guangji, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. zgj@zcmu.edu.cn Telephone: +86-13335812880; +86-13957152511; Prof. LOU Zhaohuan, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. zhaohuanlou@zcmu.edu.cn -
Supported by:Innovative Research and Application based on the Core Etiology and Pathogenesis of Different Diseases and the Same Treatment Plan based on "Blood Stasis, Toxin and Depression"(2019YFC1708700);Innovative Research and Application based on the Core Etiology and Pathogenesis of Different Diseases and the Same Treatment Plan based on "Blood Stasis, Toxin and Depression"(2019YFC1708701);Biological Basic Research on Gastric Cancer-Carcinoma Transformation and Intervention by Removing Blood Stasis and Detoxification Based on the Pathogenesis Theory of Blood Stasis and Toxin Interaction(82030119);Study on the Mechanism of Tanshinone Combined with Arsenic Trioxide Stasis and Poison to Regulate Macrophage Polarization and Improve the Inflammatory Microenvironment of Liver Cancer(81874455);Research on Innovative Traditional Chinese Medicine Drugs-preclinical Research on Anti-lung Cancer of Diterpenoid Tanshinone(2019C03072);Study on the Diagnosis and Treatment Program of Damp-heat Accumulation Type Colorectal Cancer Based on Correlation Analysis of Intestinal Microbiota- Traditional Chinese Medicine Syndrome Type(2020ZX005);Research on Quantitative Characterization of Preparation Process and Quality Standard Control Specification of Traditional Chinese Medicine Paste (Gao Zi Ji)(2019ZZ006);Study on the Molecular Mechanism of Actinidia Chinensis Polysaccharide Interfering with Epithelial Mesenchymal Transformation in Gastric Cancer by Inhibiting Nuclear Factor-κB Pathway(81273904);Study on the Mechanism of the Effective Components of Tengli Root Regulating Tumor-associated Fibroblasts to Improve the Tumor Microenvironment and Prevent the Metastasis of Gastric Cancer(2022JKZKTS16)
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ZHANG Guangshun, XU Xiaonan, XU Chuyun, LIAO Guanghui, XU Hao, LOU Zhaohuan, ZHANG Guangji. Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis[J]. Journal of Traditional Chinese Medicine, 2024, 44(5): 896-905.
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Figure 1 ACPS improved tumor inflammatory response A: histopathology of gastric cancer transplanted tumor; A1: representative picture of the model group; A2: 5-FU group; A3: ACPS-L group; A4: ACPS-H group; HE staining, × 200; B: serum levels of IL-6 in each group; C: serum levels of TGF-β in each group. 5-FU: 5-fluorouracil; ACPS: actinidia chinensis polysaccharide; ACPS-L: actinidia chinensis polysaccharide low-dose group (50 mg·kg-1·d-1); ACPS-H: actinidia chinensis polysaccharide high-dose group (100 mg·kg-1·d-1). The drug was given intraperitoneally once a day for 28 d. IL-6: interleukin-6; TGF-β: transforming growth factor beta. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 6). aP<0.01 model group vs normal group; bP<0.01 vs model group; cP<0.05 model group vs normal group.
Figure 1 ACPS improved tumor inflammatory response A: histopathology of gastric cancer transplanted tumor; A1: representative picture of the model group; A2: 5-FU group; A3: ACPS-L group; A4: ACPS-H group; HE staining, × 200; B: serum levels of IL-6 in each group; C: serum levels of TGF-β in each group. 5-FU: 5-fluorouracil; ACPS: actinidia chinensis polysaccharide; ACPS-L: actinidia chinensis polysaccharide low-dose group (50 mg·kg-1·d-1); ACPS-H: actinidia chinensis polysaccharide high-dose group (100 mg·kg-1·d-1). The drug was given intraperitoneally once a day for 28 d. IL-6: interleukin-6; TGF-β: transforming growth factor beta. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 6). aP<0.01 model group vs normal group; bP<0.01 vs model group; cP<0.05 model group vs normal group.
Figure 2 Scratch experiment was used to evaluate the effect of ACPS on the migration of BGC-823 cells A: migration at time points of 0, 6, 24, 48 h in scratch experiment; A1: control group at 0 h post-administration; A2: control group at 6 h post-administration; A3: control group at 24 h post-administration; A4: control group at 48 h post-administration; A5: EGF group at 0 h post-administration (100 ng/mL); A6: EGF group at 6 h post-administration; A7: EGF group at 24 h post-administration; A8: EGF group at 48 h post-administration; A9: ACPS group at 0 h post-administration (0.1 mg/mL); A10: ACPS group at 6 h post-administration; A11: ACPS group at 24 h post-administration; A12: ACPS group at 48 h post-administration; A13: EGF (100 ng/mL) + ACPS (0.1 mg/mL) group at 0 h post-administration; A14: EGF + ACPS group at 6 h post-administration; A15: EGF + ACPS group at 24 h post-administration; A16: EGF + ACPS group at 48 h post-administration; B: mobility of each group was compared at 48 h post-administration. EGF: epidermal growth factor; ACPS: Actinidia chinensis polysaccharide. The scratch experiment photos were collected under a 10 μm mirror. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 3). aP<0.01 vs control group.
Figure 2 Scratch experiment was used to evaluate the effect of ACPS on the migration of BGC-823 cells A: migration at time points of 0, 6, 24, 48 h in scratch experiment; A1: control group at 0 h post-administration; A2: control group at 6 h post-administration; A3: control group at 24 h post-administration; A4: control group at 48 h post-administration; A5: EGF group at 0 h post-administration (100 ng/mL); A6: EGF group at 6 h post-administration; A7: EGF group at 24 h post-administration; A8: EGF group at 48 h post-administration; A9: ACPS group at 0 h post-administration (0.1 mg/mL); A10: ACPS group at 6 h post-administration; A11: ACPS group at 24 h post-administration; A12: ACPS group at 48 h post-administration; A13: EGF (100 ng/mL) + ACPS (0.1 mg/mL) group at 0 h post-administration; A14: EGF + ACPS group at 6 h post-administration; A15: EGF + ACPS group at 24 h post-administration; A16: EGF + ACPS group at 48 h post-administration; B: mobility of each group was compared at 48 h post-administration. EGF: epidermal growth factor; ACPS: Actinidia chinensis polysaccharide. The scratch experiment photos were collected under a 10 μm mirror. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 3). aP<0.01 vs control group.
Figure 3 Immunohistochemistry was used to detect the expression of MMP9, N-cadherin and p-NF-κB p65 A: representative picture of MMP9 protein expression in each group by immunohistochemistry (DAB staining, × 200); A1: model group; A2: 5-FU group; A3: ACPS-L dose group; A4: ACPS-H dose group; B: representative picture of N-cadherin protein expression in each group by immunohistochemistry (DAB staining, × 200); B1: model group; B2: 5-FU group; B3: ACPS-L dose group; B4: ACPS-H dose group; C: representative picture of p-NF-κB p65 protein expression in each group by immunohistochemistry (DAB staining, × 200); C1: model group; C2: 5-FU group; C3: ACPS-L dose group; A4: ACPS-H dose group; D: mean OD values of MMP9 in each group were compared by immunohistochemistry; E: mean OD values of N-cadherin in each group were compared by immunohistochemistry; F: mean OD values of p-NF-κB p65 in each group were compared by immunohistochemistry. 5-FU: 5-fluorouracil; ACPS: actinidia chinensis polysaccharide; ACPS-L: actinidia chinensis polysaccharide low-dose group (50 mg·kg-1·d-1); ACPS-H: actinidia chinensis polysaccharide high-dose group (100 mg·kg-1·d-1). The drug was given intraperitoneally once a day for 28 d. MMP-9: matrix metallopeptidase 9; N-cadherin: neural cadherin; P-NFκB p65: phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 6). aP<0.01 vs model group.
Figure 3 Immunohistochemistry was used to detect the expression of MMP9, N-cadherin and p-NF-κB p65 A: representative picture of MMP9 protein expression in each group by immunohistochemistry (DAB staining, × 200); A1: model group; A2: 5-FU group; A3: ACPS-L dose group; A4: ACPS-H dose group; B: representative picture of N-cadherin protein expression in each group by immunohistochemistry (DAB staining, × 200); B1: model group; B2: 5-FU group; B3: ACPS-L dose group; B4: ACPS-H dose group; C: representative picture of p-NF-κB p65 protein expression in each group by immunohistochemistry (DAB staining, × 200); C1: model group; C2: 5-FU group; C3: ACPS-L dose group; A4: ACPS-H dose group; D: mean OD values of MMP9 in each group were compared by immunohistochemistry; E: mean OD values of N-cadherin in each group were compared by immunohistochemistry; F: mean OD values of p-NF-κB p65 in each group were compared by immunohistochemistry. 5-FU: 5-fluorouracil; ACPS: actinidia chinensis polysaccharide; ACPS-L: actinidia chinensis polysaccharide low-dose group (50 mg·kg-1·d-1); ACPS-H: actinidia chinensis polysaccharide high-dose group (100 mg·kg-1·d-1). The drug was given intraperitoneally once a day for 28 d. MMP-9: matrix metallopeptidase 9; N-cadherin: neural cadherin; P-NFκB p65: phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 6). aP<0.01 vs model group.
Figure 4 ACPS promoted p65-NF-κB nuclear transfer in BGC-823 cells and reduced the mRNA expression of MMP2, ICAM2, and VCAM1 A: expression of p65-NFκB was detected using confocal technology. A1: control group; A2: EGF group (100 ng/mL); A3: ACPS group (0.1 mg/mL); A4: EGF + ACPS group; Blue fluorescence represents nuclei stained with DAPI; The red fluorescence represents p65-NFκB; B: qPCR was used to detect MMP2 genes in each group standardized with GAPDH; C: qPCR was used to detect ICAM2 genes in each group standardized with GAPDH; D: qPCR was used to detect VCAM1 genes in each group standardized with GAPDH. Drug intervention for 48 h. p65-NFκB: p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells; DAPI: 6-diamidino-2-phenylindole; qPCR: quantitative Polymerase chain reaction; MMP2: matrix metalloproteinase-2; ICAM2: intercellular adhesion molecule 2; VCAM1: vascular cell adhesion molecule 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; EGF: epidermal growth factor; ACPS: actinidia chinensis polysaccharide. The scale bar of the above image is 25 μm. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 3). aP<0.01, EGF group vs Control group; bP<0.01, vs EGF group.
Figure 4 ACPS promoted p65-NF-κB nuclear transfer in BGC-823 cells and reduced the mRNA expression of MMP2, ICAM2, and VCAM1 A: expression of p65-NFκB was detected using confocal technology. A1: control group; A2: EGF group (100 ng/mL); A3: ACPS group (0.1 mg/mL); A4: EGF + ACPS group; Blue fluorescence represents nuclei stained with DAPI; The red fluorescence represents p65-NFκB; B: qPCR was used to detect MMP2 genes in each group standardized with GAPDH; C: qPCR was used to detect ICAM2 genes in each group standardized with GAPDH; D: qPCR was used to detect VCAM1 genes in each group standardized with GAPDH. Drug intervention for 48 h. p65-NFκB: p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells; DAPI: 6-diamidino-2-phenylindole; qPCR: quantitative Polymerase chain reaction; MMP2: matrix metalloproteinase-2; ICAM2: intercellular adhesion molecule 2; VCAM1: vascular cell adhesion molecule 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; EGF: epidermal growth factor; ACPS: actinidia chinensis polysaccharide. The scale bar of the above image is 25 μm. The statistical method used in this figure is one-way analysis of variance. Results are presented as mean ± standard deviation (n = 3). aP<0.01, EGF group vs Control group; bP<0.01, vs EGF group.
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