Abstract
Hepatocellular carcinoma (HCC) accounts for many cases of cancer-associated mortality. Tumor necrosis factor (TNF)-α is a key mediator of tumor-promoting inflammation. It has been demonstrated that anti-TNF-α treatments have preclinical benefits for multiple types of cancer, however their potential for treating HCC remains unclear. Through fluorescence-activated cell sorter analysis and enzyme-linked immunosorbent assay, the results of the current study indicated that TNF-α was strongly expressed in HCC tissues and the HCC cell lines HepG2 and Hep3B. In vitro, anti-TNF-α antibodies (infliximab and etanercept) decreased HCC cell viability via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity effects. Infliximab treatment also significantly increased apoptosis in HepG2 and Hep3B cells compared with controls (P<0.001 and P<0.05, respectively). In vivo, anti-TNF-α treatment delayed HCC progression as indicated by the significantly prolonged survival time in an HCC xenograft mouse model (P=0.0009). Further analyses revealed that anti-TNF-α treatment significantly decreased the expression of pro-inflammatory cytokines, including TNF-α (P<0.01), interleukin (IL)-1β (P<0.05), IL-6 (P<0.05) and IL-17 (P<0.05) and induced apoptosis in HCC tumors. The results of the current study suggest that TNF-α is a potential target for novel therapeutic strategies to treat HCC. Anti-TNF-α treatments compromised HCC tumor progression by inducing cell death and decreasing levels of pro-inflammatory cytokines.