Dexamethasone induced apoptosis of A549 cells via the TGF-β1/Smad2 pathway.

Lung cancers are the most commonly diagnosed malignant tumors, and are one of the leading causes of morbidity and mortality worldwide. Dexamethasone (DEX) serves an important function in the regulation of lung cancer cell proliferation; however, the mechanisms involved still remain unknown. In the present study, the effects of DEX on A549 cell proliferation and apoptosis were examined, in addition to the potential downstream regulatory mechanisms underlying these effects. A549 cells were treated with different concentrations of DEX at 12, 24 and 48 h time points, followed by the addition of SB431542, an inhibitor of the TGF-β1 receptor, to block the TGF-β1 signaling pathway. Cell proliferation was analyzed using a 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt. The apoptosis rate was measured by Hoechst 33342 and Annexin V/propidium iodide staining and the expression of transforming growth factor (TGF)-β1, Smad family member 2 (Smad2) and caspase-3 were assessed by western blot. The results from the present study demonstrated that the proliferation of A549 cells decreased and the apoptosis rate significantly increased following DEX treatment (P<0.05). Furthermore, the expression of TGF-β1, Smad2 and caspase-3 were significantly increased following DEX stimulation (P<0.05), the effects of which were abrogated by the addition of the TGF-β1 receptor inhibitor, SB431542 (P<0.05). DEX-induced apoptosis in A549 cells, and this effect was abrogated by SB431542, an inhibitor of TGF-β1 receptor signaling, which indicated that the TGF-β1/Smad2 pathway may be associated with this process and SB431542 may function as an antitumor drug in the future.