TNF-α promotes gallbladder cancer cell growth and invasion through autocrine mechanisms

Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be a putative tumor promoter gene, and autocrine of TNF-alpha expression has been found in colon cancer and ovarian cancer. As the role of autocrine TNF-alpha in human gallbladder cancer has not yet been elucidated, the present study examined the expression of TNF-alpha in gallbladder cancer-derived cell lines. Based on the data, TNF-alpha mRNA and TNF-alpha protein expression differed significantly different between the cell lines. In addition, using siRNA targeting TNF-alpha, the vector, pGPU-GFP-siTNF-alpha, was constructed and then transfected into the SGC-996 cells (gallbladder cancer cell line) which express high levels of endogenous TNF-alpha. In vitro experiments indicated that the silencing of TNF-alpha in the SGC-996 cells significantly suppressed proliferation and invasion. However, apoptosis was not induced by the silencing of TNF-alpha. Furthermore, we traced the mechanisms underlying these effects and found that the silencing of TNF-alpha affected the TNF-alpha-AKT-NF-kappa B-Bcl-2 pathway in the SGC-996 cells. Our data provide evidence that autocrine TNF-alpha plays a role as a tumor promoter gene in gallbladder cancer cells, possibly by promoting proliferation and invasion through autocrine mechanisms.