C‐Myc participates in β‐catenin–mediated drug resistance in A549/DDP lung adenocarcinoma cells

The aim of this study was to investigate c‐Myc and β‐catenin–mediated drug resistance in A549/ DDP lung adenocarcinoma cells. Cisplatin sensitivity was determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide ( MTT ) toxicity assay. β‐Catenin and c‐Myc protein expression following cisplatin treatment were determined using western blotting and immunofluorescence. Flow cytometry was performed to detect cell cycle and apoptosis in A549, A549/ DDP , and c‐Myc small interfering RNA (si RNA )–transfected A549/ DDP cells before and after treatment with different doses of cisplatin. The median inhibitory concentration ( IC 50 ) in cisplatin‐treated A549 and A549/ DDP cells was 5.769 ± 0.24 μmol/L and 28.373 ± 0.96 μmol/L, respectively; the cisplatin resistance of A549 cells was about five times that of A549/ DDP cells. Endogenous β‐catenin and c‐Myc expression in A549/ DDP cells were higher than that in A549 cells, and were upregulated in A549/ DDP cells ( p  <   0.05) and downregulated in A549 cells after 48 h cisplatin treatment ( p  <   0.05). β‐catenin localization transferred from membrane/cytoplasmic/nuclear to cytoplasmic/nuclear, and c‐Myc localization transferred from cytoplasmic/nuclear to nuclear in both cell lines following cisplatin treatment. The rate of apoptosis increased in a dose‐dependent manner with cisplatin. After 48‐h transfection with c‐myc si RNA , A549/ DDP cells were blocked in the S phase, and G0/G1‐phase cells increased. Simultaneously, the apoptotic rate was increased ( p  <   0.05) and the IC 50 decreased significantly ( p  <   0.05). C‐myc, the downstream target gene of β‐catenin, plays an important role in regulating cisplatin resistance in A549/ DDP cells. C‐Myc si RNA improved the sensitivity of A549/ DDP cells to cisplatin.