Radiosensitisation of bladder cancer cells by panobinostat is modulated by Ku80 expression.
Bottom Line: Resolution of γH2AX foci was determined by immunofluorescence confocal microscopy, cell cycle progression by FACS analysis and protein expression by western blotting.PAN had a greater radiosensitising effect in Ku80KD than RT112 or RAD51KD cells; enhancement ratios 1.35 for Ku80KD at 10nM (IC(20) for Ku80KD) and 1.31 for RT112 and RAD51KD at 25 nM (IC(40) for both).As muscle-invasive bladder tumours have reduced Ku-DNA binding, PAN could be particularly useful as a radiosensitiser in bladder cancer.
Affiliation: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, United Kingdom.Show MeSH
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Mentions: First, we determined the inhibitory effect of panobinostat (PAN) on growth of RT112, RAD51KD, Ku80KD and NSC cells by clonogenic assay. After 24 h treatment, IC50 values for PAN were 27 nM in RT112, 25 nM in RAD51KD, 19 nM in Ku80KD and 27 nM in NSC cells; it was therefore more toxic in Ku knockdown cells (Fig. 1A and Supplementary Fig. 1A).
Affiliation: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, United Kingdom.