paquinimod  (MedChemExpress)

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Neutrophil-macrophage crosstalk via NETs–IL-17/VEGF/S100A9 axis promotes hepatocellular carcinoma progression

doi: 10.1186/s13046-025-03618-x

Figure Lengend Snippet: M2 macrophage-derived VEGF induces neutrophil NETs formation by indirectly promoting HCC cell-derived S100A9. A Western blot analysis for CitH3 expression in neutrophils treated with and without CM-M0, CM-HuH-7, CM-(HuH-7 + M0), or CM-(HuH-7 + M0 + NETs) for 12 h. Densitometric values were normalized to β-actin and compared to the control group, with quantification shown in the right panel. M0 denotes THP-1-derived M0. B Representative IF images of DNA/MPO/CitH3 staining in neutrophils subjected to the same treatments as shown in A. C Western blot analysis for S100A9 expression in HuH-7 cells treated with CM-(HuH-7 + M0) or CM-(HuH-7 + M0 + NETs) for 24 h. Densitometric values were normalized to β-actin and compared to the control group, with quantification shown in the right panel. M0 denotes THP-1-derived M0. D ELISA analysis of S100A9 levels in the culture supernatant of HuH-7 cells, using the same grouping as described in C. E Western blot analysis of CitH3 expression in neutrophils following 12 h treatment with CM-(HuH-7-M0) or CM-(HuH-7-M0 + NETs), with or without Paquinimod. Densitometric values were normalized to β-actin and compared to the control group, with quantification shown in the right panel. M0 denotes THP-1-derived M0. F Representative IF images of DNA/MPO/CitH3 staining in neutrophils subjected to the same treatments as described in E. G Western blot analysis for S100A9, p-p65(S536), and p65 expression in HuH-7 cells treated with CM-(HuH-7-M0 + NETs), with or without AV-951 for 24 h. Densitometric values were normalized to β-actin and compared to the control group, with quantification presented in the right panel. M0 denotes THP-1-derived M0. H Western blot analysis of S100A9, p-p65(S536), and p65 expression in HuH-7 cells treated with or without exogenous VEGF, with or without BAY11-7082 for 24 h. Densitometric values were normalized to β-actin and compared with the control group, with quantification shown in the right panel. I Correlation analysis between serum MPO-DNA levels and NETs-IL-17 levels in HCC patients. J Correlation analysis between NETs-IL-17 levels and serum levels of VEGF in HCC patients. K Correlation analyses between serum levels of VEGF and S100A9 in HCC patients. L Correlation analyses between serum levels of S100A9 and MPO-DNA in HCC patients White scale bars: 30 μm. Data are presented as mean ± SD. Ns, not significant. * p < 0.05, ** p < 0.01, *** p < 0.001. One-way ANOVA followed by the Newman-Keuls multiple comparison test (A, C, D, E, H); Student’s t test (G)

Article Snippet: NF-κB inhibitor BAY11-7082 (10 μM; MedChemExpress, USA), S100A9 inhibitor Paquinimod (25 μM; MedChemExpress, USA), and VEGFR inhibitor AV-951 (100 nM; MedChemExpress, USA).

Techniques: Derivative Assay, Western Blot, Expressing, Control, Staining, Enzyme-linked Immunosorbent Assay, Comparison

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Neutrophil-macrophage crosstalk via NETs–IL-17/VEGF/S100A9 axis promotes hepatocellular carcinoma progression

doi: 10.1186/s13046-025-03618-x

Figure Lengend Snippet: The clinical significance of NETs-IL-17 in HCC patients. A ROC curve of serum NETs, NETs-IL-17, serum VEGF and serum S100A9 for identifying advanced stage from early stage in HCC patients. B ROC curve of serum NETs, NETs-IL-17, serum VEGF and serum S100A9 for predicting metastasis in HCC patients. C ROC curve of serum NETs, NETs-IL-17, serum VEGF and serum S100A9 for predicting extrahepatic metastasis in HCC patients. D Schematic illustration of the proposed working model: IL-17 carried by NETs activates the IL-17/NF-κB signaling pathway, promoting the polarization of M2d macrophages. These polarized M2d macrophages secrete VEGF, which stimulates HCC cells to produce S100A9. S100A9, in turn, induces neutrophils to release additional NETs, thereby establishing a positive feedback loop

Article Snippet: NF-κB inhibitor BAY11-7082 (10 μM; MedChemExpress, USA), S100A9 inhibitor Paquinimod (25 μM; MedChemExpress, USA), and VEGFR inhibitor AV-951 (100 nM; MedChemExpress, USA).

Techniques: