Effect of β-catenin silencing in overcoming radioresistance of head and neck cancer cells by antagonizing the effects of AMPK on Ku70/Ku80

ABSTRACT Background We attempted to elucidate the mechanism of cell death after radiation by studying how β‐catenin silencing controls the radiation sensitivity of radioresistant head and neck cancer cells. Methods The most radioresistant cancer cell line (AMC‐HN‐9) was selected for study. Targeted silencing of β‐catenin was used on siRNAs. Sensitivity to radiation was examined using clonogenic and methylthiazol tetrazolium (MTT) assays. Results A combination of irradiation plus β‐catenin silencing led to a significant reduction in the inherent radioresistance of AMC‐HN‐9 cells. Although expression of Ku70/80 was upregulated in AMC‐HN‐9 cells after irradiation, Ku70/80 was dramatically decreased in a combination of irradiation and β‐catenin silencing. Interestingly, irradiation‐induced Ku70/80 was completely prevented by β‐catenin silencing‐induced LKB1/AMP‐activated protein kinase (LKB1/AMPK) signal. Conclusion The LKB1/AMPK pathway might relay the signal between the Wnt/β‐catenin pathway and the Ku70/Ku80 DNA repair machinery, and play a decisive role in fine‐tuning the responses of cancer cells to irradiation. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1909–E1917, 2016