C‐Myc participates in β‐catenin–mediated drug resistance in A549/DDP lung adenocarcinoma cells. Issue 12 (6th August 2014)

• Record Type: Journal Article
• Authors: Xie, Chengyao; Pan, Yongqi; Hao, Fengxia; Gao, Yuan; Liu, Zan; Zhang, Xiuwei; Xie, Lingling; Jiang, Guiyang; Li, Qingchang; Wang, Enhua
• Is Part Of: Apmis. Volume 122:Issue 12(2014:Dec.)
• Page Start: 1251
• Page End: 1258
• Publication Date: 2014-08-06
• Subjects: Pathology -- Periodicals; Microbiology -- Periodicals; Immunology -- Periodicals; 572
• DOI: 10.1111/apm.12296
• Languages: English
• ISSNs: 0903-4641

Abstract

<abstract abstract-type="main" id="apm12296-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 (siRNA)–transfected A549/DDP cells before and after treatment with different doses of cisplatin. The median inhibitory concentration (IC<sub>50</sub>) 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 (<italic>p </italic><<italic> </italic>0.05) and downregulated in A549 cells after 48 h cisplatin treatment (<italic>p </italic><<italic> </italic>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 siRNA, A549/DDP cells were blocked in the S phase, and G0/G1‐phase cells increased. Simultaneously, the apoptotic rate was increased (<italic>p </italic><<italic> </italic>0.05) and the IC<sub>50</sub> decreased significantly (<italic>p </italic><<italic> </italic>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 siRNA improved the sensitivity of A549/DDP cells to cisplatin.</p> </abstract>