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

Zhu,Guangwei; Du,Qiang; Wang,Xiaoqian; Tang,Nanhong; She,Feifei; Chen,Yanling

doi:10.3892/ijmm.2014.1711

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

Authors:
- Guangwei Zhu
- Qiang Du
- Xiaoqian Wang
- Nanhong Tang
- Feifei She
- Yanling Chen
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Affiliations: Department of Hepatobiliary Surgery, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, Fujian, P.R. China, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, P.R. China
Published online on: March 24, 2014 https://doi.org/10.3892/ijmm.2014.1711
Pages: 1431-1440
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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

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