Zhu Guangwei, Du Qiang, Wang Xiaoqian, Tang Nanhong, She Feifei, Chen Yanling
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.
Int J Mol Med. 2014 Jun;33(6):1431-40. doi: 10.3892/ijmm.2014.1711. Epub 2014 Mar 24.
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.
肿瘤坏死因子-α（TNF-α）被认为是一种假定的肿瘤促进基因，并且在结肠癌和卵巢癌中已发现TNF-α表达的自分泌现象。由于自分泌TNF-α在人类胆囊癌中的作用尚未阐明，本研究检测了TNF-α在胆囊癌衍生细胞系中的表达。基于这些数据，各细胞系之间TNF-α mRNA和TNF-α蛋白表达存在显著差异。此外，使用靶向TNF-α的小干扰RNA（siRNA）构建了载体pGPU-GFP-siTNF-α，然后将其转染到表达高水平内源性TNF-α的SGC-996细胞（胆囊癌细胞系）中。体外实验表明，SGC-996细胞中TNF-α的沉默显著抑制了细胞增殖和侵袭。然而，TNF-α的沉默并未诱导细胞凋亡。此外，我们追踪了这些效应的潜在机制，发现TNF-α的沉默影响了SGC-996细胞中的TNF-α-AKT-NF-κB-Bcl-2信号通路。我们的数据提供了证据，表明自分泌TNF-α在胆囊癌细胞中作为肿瘤促进基因发挥作用，可能是通过自分泌机制促进细胞增殖和侵袭。
