SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis.
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ABSTRACT: The role of tumor necrosis factor alpha (TNF-?) 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-? on the activation and expression of nuclear factor kappa B (NF-?B)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-?-induced apoptosis.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-? treatment for 24-48 h.We found the NF-?B activity and PUMA mRNA/protein was significantly increased after treatment of TNF-? for 24 h in untreated A549 cells, and led to a significant increase in TNF-?-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-? for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-?-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-? for 24 h. Inhibition of the NF-?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-?-induced apoptosis after treatment of TNF-? for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-?-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level.The findings suggested that TNF-? treatment promoted apoptosis via the NF-?B-dependent PUMA pathway. The anti-apoptotic role of TNF-? was via NF-?B-dependent SLUG and Bcl-2 pathway at a later time.
SUBMITTER: Wang Y
PROVIDER: S-EPMC3561261 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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