Abstract 508: Synergistic effect of β-catenin knockdown and radiation combination toward AMC-HN9 head and neck cancer cells is associated with down-regulation of Ku expression.

Abstract

Abstract Based on our previous report showing that up-regulation of Ku70/Ku80 in AMC-HN9 (HN9) cells is required for cell-cycle re-entry and cell proliferation following irradiation, further study to investigate the mechanism by which β-catenin knockdown sensitizes the cells to irradiation have been conducted. β-Catenin, as a multifunctional protein involved in cadherin-mediated cell-cell adhesion and Wnt signaling transduction, have been well known to regulates cell growth and survival following radiation in various types of cancer cells. However, the molecular mechanisms by which β-catenin affects radiation sensitivity are still not fully understood, which led us to explore, with regard to regulation of Ku70/Ku80 expression, the molecular mechanism of the synergistic effects of β-catenin silencing and radiation combination in radio-resistant head and neck cancer cells. β-Catenin silencing using small interfering RNA(siRNA) down-regulated β-catenin expression up to 72 h both in membranous and nuclear fraction of HN9 cells. β-Catenin knockdown induced cell cycle arrest on G1 phase and thus decreased cell proliferation, but didn't cause any DNA damage response and cell death. Whereas expression of Ku70/Ku80 was up-regulated in HN9 cell following irradiation (4Gy), in the cells treated with combination of radiation and β-catenin siRNA, Ku70/Ku80 expression were dramatically decreased. In addition, when β-catenin silenced cells were exposed to single dose of radiation, irradiation-induced cell death was much more increased from 3.1% to 13% and accompanied with caspase-3 activation and PARP cleavage. Taken together, these results suggest that inhibition of Ku expression through β-catenin silencing is associated with its radio-sentitizing effect in HN9 cells and further studies to clarify the pathway linking β-catenin signaling and regulation of Ku70/Ku80 expression are warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 508.