Dexamethasone Inhibits TRAIL- and Anti-cancer Drugs-induced Cell Death in A549 Cells through Inducing NF-kappaB-independent cIAP2 Expression
Dexamethasone Inhibits TRAIL- and Anti-cancer Drugs-induced Cell Death in A549 Cells through Inducing NF-κB-independent cIAP2 Expression
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Abstract
Purpose: We have examined that dexamethasone inhibits apoptotic cell death of A549 lung epithelial cells through TRAIL and anti-cancer drugs. The purpose of the study is to determine the roles of GR, cIAP and NF-KappaB in this mechanism. Materials and Methods: In the A549 lung epithelial cell line, TRAIL, taxol, doxorubicine & gemcitabine were used to investigate cell toxicity. Cells were pretreated 12 hours in advance with dexamethasone. RU486 was pretreated 30 minutes before dexamethasone. Crystal violet assay was used for cell toxicity tests. Apoptosis assay was performed by taking morphologic surveys with fluorescent microscopy after double staining with Hoechst 33342 & propium iodide. RT-PCR was used to investigate the gene expression of cIAP1 & cIAP2 by dexamethasone. Ad-IKappaBalpha-SR transduction study was used for the role of NF-KappaB. Results: TRAIL and anti-cancer drug-induced apoptosis was partially suppressed in A549 cells pretreated with dexamethasone. The inhibitory effect on cell death disappeared in A549 cells pretreated with RU486. Using RT-PCR, changes of cIAP1 and cIAP2 genes manifestation in A549 cells subsequent to pretreatment with dexamethasone were examined. The results showed an increase in cIAP2 expression during a course of time which was suppressed by RU486 pretreatment. Induction of cIAP2 expression changes by dexamethasone was uniquely observed despite the blockade of NF-KappaB by Ad-Ikappa Balpha-SR transduction. Conclusions: These results suggest that dexamethasone inhibits TRAIL- and anti-cancer drug-induced apoptosis in A549 cells by inducing cIAP2 gene expression through a GR-mediated, NF-KappaB-independent pathway.(Cancer Res Treat. 2004;36:330-337)
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