Fig. 8

INHBB promotes GC progression in vivo. (A) The quantitative analysis of tumor weight from MGC-803 cells with stable INHBB knockdown or vehicle control (n = 4). (B) The growth curve of tumor volume from MGC-803 cells with stable INHBB knockdown or vehicle control (n = 4). (C) The quantitative analysis of tumor weight from HGC-27 cells with stable INHBB overexpressing or vehicle control (n = 5). (D) The growth curve of tumor volume from HGC-27 cells with stable INHBB overexpressing or vehicle control (n = 5). (E) The expression of collagen, a-SMA, Vimentin, IL-1B and p-p65 were evaluated by IHC in tissues of xenograft. (F) The quantitative analysis of tumor weight from MGC-803 shINHBB cells with IL-1b treatment or control treatment (n = 4). (G) The growth curve of tumor volume from MGC-803 shINHBB cells with IL-1b treatment or control treatment (n = 4). (H) The quantitative analysis of tumor weight from HGC-27 INHBB cells with JSH-23 treatment or control treatment (n = 5). (I) The growth curve of tumor volume from HGC-27 INHBB cells with JSH-23 treatment or control treatment (n = 5). (J) The expression of p-p65 and INHBB in tissues of xenograft. K. Diagrammatic presentation of the INHBB/NF-kB/IL-1b positive regulatory feedback loop between GC cells and fibroblasts that can promote GC progression. Activin B, the dimer structure formed by INHBB subunit, activates NF-kB pathway by controlling the autoubiquitination of TRAF6 and inducing TAK1 phosphorylation in fibroblasts. Activation of NF-kB releases IL-1b, which facilitates the phosphorylation of p65 and increases GC cells proliferation and invasion. Furthermore, p65 directly promotes INHBB transcription and induces INHBB expression, establishing a positive- feedback loop in GC microenvironment. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001