Antitumor necrosis factor‑α antibodies as a novel therapy for hepatocellular carcinoma

Li,Wei; Jian,Yong‑Bin

doi:10.3892/etm.2018.6235

Antitumor necrosis factor‑α antibodies as a novel therapy for hepatocellular carcinoma

Authors:
- Wei Li
- Yong‑Bin Jian
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Affiliations: Interventional Medical Center, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266555, P.R. China, Department of Interventional Radiology, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
Published online on: May 30, 2018 https://doi.org/10.3892/etm.2018.6235
Pages: 529-536
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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