Expression and function of transforming growth factor-β-activated protein kinase 1 in gastric cancer

The present study aimed to investigate the expression and role of transforming growth factor (TGF) -β-activated protein kinase 1 (TAK1) in human gastric cancer. Immunohistochemistry was performed to investigate the expression of TAK1 in surgical specimens of human gastric cancer tissue and adjacent normal tissue. The association between TAK1 and clinicopathologic factors was analyzed and the association between TAK1 expression and the overall survival rates was evaluated using Kaplan-Meier curves. In addition, the effect of the TAK1 selective inhibitor 5Z-7-oxozeaenol (OZ) on the biological characteristics of MGC803 human gastric cancer cells in vitro were investigated. The role of TAK1 in gastric cancer cell proliferation, apoptosis and invasion were determined by cell proliferation assays, flow cytometry analysis and transwell invasion assays, respectively. The findings of the present study demonstrated that the positive expression rate of TAK1 in gastric cancer and adjacent normal tissues was 70.5 and 25.9%, respectively. Furthermore, TAK1 expression was significantly associated with advanced N stage and pathological stage (P<0.05). Survival analysis of 139 patients with gastric cancer indicated a lower overall survival rate of patients in the TAK1-positive group compared with the TAK1-negative group (P<0.05). In addition, treatment with the TAK1 selective inhibitor OZ reduced the proliferation and invasion abilities of MGC803 cells and significantly reduced the expression levels of phosphorylated-TAK1 (Thr187), nuclear p65, cyclin D1, Bcl-2 apoptosis regulator and matrix metallopeptidase (MMP)9 (P<0.05). OZ treatment significantly increased the expression levels of cytosolic cytochrome c and cleaved caspase 3 and the apoptosis rate in MGC803 cells (P<0.05). In conclusion, these findings suggest that increased TAK1 expression may be involved in the progression of gastric cancer; therefore, TAK1 may be used as a future therapeutic target for gastric cancer treatment.