%0 Journal Article
%T SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis
%A Wang Yaopeng
%A Yue Bin
%A Yu Xuyi
%A Wang Zhan
%J World Journal of Surgical Oncology
%D 2013
%I BioMed Central
%R 10.1186/1477-7819-11-12
%X Background The role of tumor necrosis factor alpha (TNF-汐) in cancer is complex with both apoptotic and anti-apoptotic roles proposed. However the mechanism is not clear. In the study, we designed to investigate the effect of TNF-汐 on the activation and expression of nuclear factor kappa B (NF-百B)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-汐-induced apoptosis. Methods We have engineered three A549 cell lines that were transiently transfected with PUMA siRNA, SLUG siRNA and Bcl-2 siRNA, respectively. We have measured the in vitro effects of siRNA on apoptosis, and sensitivity to 20 ng/ml of TNF-汐 treatment for 24每48 h. Results We found the NF-百B activity and PUMA mRNA/protein was significantly increased after treatment of TNF-汐 for 24 h in untreated A549 cells, and led to a significant increase in TNF-汐-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-汐 for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-汐-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-汐 for 24 h. Inhibition of the NF-百B activity could effectively decrease the PUMA level and increase the SLUG and Bcl-2 level. PUMA silencing by siRNA led to a significant decrease in TNF-汐-induced apoptosis after treatment of TNF-汐 for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-汐-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level. Conclusions The findings suggested that TNF-汐 treatment promoted apoptosis via the NF-百B-dependent PUMA pathway. The anti-apoptotic role of TNF-汐 was via NF-百B-dependent SLUG and Bcl-2 pathway at a later time.
%K TNF-汐
%K NF-百B
%K PUMA
%K SLUG
%K Bcl-2
%K apoptosis
%U http://www.wjso.com/content/11/1/12