Abstract # 1049 Histone Deacetylase Inhibitor LBH589 Radiosensitizes Non-Small Cell Lung Cancer by Inhibiting DNA Repair

Presenter: Cuneo, Kyle

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Treatment with 25 nM LBH589 for 1 h and 18 h prior to 0-6 Gy sensitized NSCLC to the cytotoxic effects of ionizing radiation in clonogenic survival assays. Additionally, Annexin-PI staining revealed that LBH589 synergistically enhanced radiation induced apoptosis to 30% compared to 7% for 3 Gy alone and 2% for LBH589 alone. This effect was confirmed with DAPI nuclear morphology and cleaved caspase 3 Western blot analysis. In vivo tumor growth studies showed a tumor growth delay of 20 days for combined treatment compared to 2 days for LBH589 and 4 days for radiaiton alone. Furthermore, immunostaining for γ-H2AX nuclear foci revealed a synergistic effect of LBH589 and radiation on prolonging γ-H2AX foci resolution 24 h after treatment indicating that this molecule inhibits the DNA repair process (see figure). It was further shown that 3 Gy induced nuclear localization of HDAC4 and that this process was completely attenuated with LBH589 treatment prior to radiation.

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