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: RAD51, Ku70/80 and histone H3K18 expression were measured by Western blot after 25 nM PAN ± 5 Gy (Fig. 3). RAD51 and Ku80 levels were reduced as expected in the respective knockdown cells. PAN reduced RAD51 levels in all cell lines and attenuated the RAD51 upregulation seen after 5 Gy. Ku70 and Ku80 protein levels were not markedly affected by PAN treatment.
Affiliation: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, United Kingdom.