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

被引:79
作者
Zhu, Guangwei [1 ,2 ]
Du, Qiang [1 ,2 ]
Wang, Xiaoqian [1 ]
Tang, Nanhong [1 ]
She, Feifei [2 ,3 ]
Chen, Yanling [1 ,2 ]
机构
[1] Fujian Med Univ, Dept Hepatobiliary Surg, Affiliated Union Hosp, Fuzhou 350001, Fujian, Peoples R China
[2] Fujian Med Univ, Key Lab, Minist Educ Gastrointestinal Canc, Fuzhou 350001, Fujian, Peoples R China
[3] Fujian Med Univ, Key Lab Tumor Microbiol, Sch Basic Med Sci, Fuzhou 350001, Fujian, Peoples R China
基金
中国国家自然科学基金;
关键词
gallbladder cancer cell; tumor necrosis factor-alpha; siRNA; autocrine; proliferation; invasion; apoptosis; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; OVARIAN-CANCER; MESENCHYMAL TRANSITION; EXPRESSION; INVASIVENESS; MACROPHAGES; METASTASIS; ACTIVATION; RECEPTOR-1;
D O I
10.3892/ijmm.2014.1711
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
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.
引用
收藏
页码:1431 / 1440
页数:10
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