Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways

A disintegrin and metalloproteinase 17 (ADAM17) is highly expressed in various tumours and affects tumour progression. In this study, ADAM17 expression in 60 gastric cancer and 20 normal gastric mucosal tissues was assessed using immunohistochemistry. ADAM17 expression was higher in gastric cancer tissues than in normal gastric mucosal tissues (P < 0.0005). A significant relationship was identified between ADAM17 expression and the depth of tumour invasion, metastasis, and carcinoma stage. Furthermore, the effects of ADAM17 knockdown on the proliferation, cell invasion, and apoptosis of human gastric carcinoma cells (SGC-7901) were determined. SGC-7901 cells were transfected with ADAM17-shRNA, and cell proliferation and migration were assessed using CCK-8 and transwell assays, respectively, to evaluate the role of ADAM17 in tumour proliferation and invasion. Furthermore, the EGFR signalling pathway, the cell membrane receptor-bound TNF-alpha level, and apoptosis were evaluated by western blotting and flow cytometry. The inhibition of cell proliferation and invasion was observed in the ADAM17 knockdown cells, which was associated with modulation of the EGFR signalling pathway. Apoptosis was increased, and TNF-alpha signalling was attenuated in the ADAM17 knockdown cells. Our study demonstrated that ADAM17 over-expression in gastric cancer tissues was closely associated with tumour proliferation, invasion, and apoptosis.