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

Background. We attempted to elucidate the mechanism of cell death after radiation by studying how beta-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 beta-catenin was used on siRNAs. Sensitivity to radiation was examined using clonogenic and methylthiazol tetrazolium (MTT) assays. Results. A combination of irradiation plus beta-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 beta-catenin silencing. Interestingly, irradiation-induced Ku70/80 was completely prevented by beta-catenin silencing-induced LKB1/AMP-activated protein kinase (LKB1/AMPK) signal. Conclusion. The LKB1/AMPK pathway might relay the signal between the Wnt/beta-catenin pathway and the Ku70/Ku80 DNA repair machinery, and play a decisive role in fine-tuning the responses of cancer cells to irradiation. (C) 2015 Wiley Periodicals, Inc.