Abstract 4904: β-catenin silencing enhances radiation sensitivity through antagonizing effect of AMPK against Ku70/80 in head and neck cancer cells

Abstract

Abstract The Wnt/β-catenin pathway regulates the cell growth and survival following radiation in various types of cancer cells. Our previous report show that activation of the Wnt/β-catenin signaling pathway is a key radioprotective mechanism in irradiated head and neck cancer (HNC) cells. However, the molecular mechanisms by which β-catenin regulates radiation sensitivity are not clear. Here we attempted to elucidate the mechanism of cell death following radiation by studying how β-catenin silencing controls the radiation sensitivity of radioresistant HNC cells. Of nine cell lines examined, the most radioresistant cell line (AMC-HN-9) were selected for this experiments. β-catenin silencing using small interfering RNA(siRNA) down-regulated β-catenin expression up to 72 h, which was confirmed by western blot analysis. The sensitivity to radiation was anlayzed by clonogenic analysis and MTT assay. As a result, β-catenin silencing remarkably decreased the survival of irradiated AMC-HN-9 cells and the cell viability also significantly reduced more by the combination treatment with β-catenin siRNA and radiation (0.37±0.034 fold) than when treated with β-catenin siRNA or radiation alone (0.68±0.055 fold and 0.90±0.043 fold, respectively). Interestingly, whereas expression of Ku70/80 was up regulated in AMC-HN-9 cells following irradiation (4Gy), in the cells treated with combination of radiation and β-catenin siRNA, Ku70/80 expression was dramatically decreased. In additionally, when exposed to radiation after β-catenin silencing, the up-regulation of irradiation-induced Ku80 completely was prevented by β-catenin silencing-induced AMPK. Taken together, these results suggest that suppression of Ku70/80 expression through β-catenin silencing-induced AMPK is associated with its radio-sentitizing effect in AMC-HN-9 cells, thus supporting a novel radiosensitive mechanism of radioresistant HNC cells. Citation Format: Hyo Won Chang, Hae Yun Nam, Mi Ra Kim, Hyang Ju Lee, Ji Hyun Seo, So Yeon Lee, Seong Who Kim, Sang Yoon Kim. β-catenin silencing enhances radiation sensitivity through antagonizing effect of AMPK against Ku70/80 in head and neck cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4904. doi:10.1158/1538-7445.AM2014-4904