Fig. 6

ADAM17 selective inhibitor JG26 and oral inhibitor aderbasib effectively reduce colorectal cancer (CRC) metastasis in vivo. (a) Schematic illustration of the tumor metastasis experiments used to assess EMT-HCT116-Exo-treated mice that were administered ADAM17 selective inhibitor JG26 (3 mg/kg, IV) and ADAM17 oral inhibitor aderbasib (30 mg/kg, PO). (b) Representative immunohistochemistry staining for VE-cadherin and immunofluorescence staining of CD34/VE-cadherin at the invasive front in mice with CRC (black scale bar = 50 μm, white scale bar = 25 μm). (c) Relative VE-cadherin level at the invasive front (n = 10) and CTC counts (n = 20) in EMT-HCT116-Exo-treated mice (3 mg/kg JG26, IV; 30 mg/kg aderbasib, PO). (d) Representative H&E staining results of lung sections from EMT-HCT116-Exo-treated mice (3 mg/kg JG26, IV; 30 mg/kg aderbasib, PO). Arrows indicate tumor nodules. Scale bar = 250 μm. (e) Evans blue accumulation in the lung parenchyma (n = 8). (f) Percentage of mice with lung metastasis, alongside the number and maximal diameter of metastatic nodules in the lungs of EMT-HCT116-Exo-treated mice (3 mg/kg JG26, IV; 30 mg/kg aderbasib, PO). (g) Representative H&E staining results of liver sections from EMT-HCT116-Exo-treated mice (3 mg/kg JG26, IV; 30 mg/kg aderbasib, PO). Arrows indicate tumor nodules. Scale bar = 250 μm. (h) Evans blue accumulation in the liver parenchyma (n = 8). (i) Percentage of mice with liver metastasis, alongside the number and maximal diameter of metastatic nodules in the liver of EMT-HCT116-Exo-treated mice (3 mg/kg JG26, IV; 30 mg/kg aderbasib, PO). Data are expressed as mean ± standard deviation. *P < 0.05, **P < 0.01, compared with the control group; #P < 0.05, ##P < 0.01, compared with the EMT-HCT116-Exo group