SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis
The role of tumor necrosis factor alpha (TNF-α) 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-α on the activation and expression of nuclear factor kappa B (NF-κB)/p65/SLUG/PUM...
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Veröffentlicht in: | World journal of surgical oncology 2013-01, Vol.11 (1), p.12-12, Article 12 |
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Zusammenfassung: | The role of tumor necrosis factor alpha (TNF-α) 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-α on the activation and expression of nuclear factor kappa B (NF-κB)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-α-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-α treatment for 24-48 h.
We found the NF-κB activity and PUMA mRNA/protein was significantly increased after treatment of TNF-α for 24 h in untreated A549 cells, and led to a significant increase in TNF-α-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-α for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-α-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-α for 24 h. Inhibition of the NF-κB 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-α-induced apoptosis after treatment of TNF-α for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-α-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level.
The findings suggested that TNF-α treatment promoted apoptosis via the NF-κB-dependent PUMA pathway. The anti-apoptotic role of TNF-α was via NF-κB-dependent SLUG and Bcl-2 pathway at a later time. |
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ISSN: | 1477-7819 1477-7819 |
DOI: | 10.1186/1477-7819-11-12 |