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Radiosensitisation of bladder cancer cells by panobinostat is modulated by Ku80 expression.

Groselj B, Kerr M, Kiltie AE - Radiother Oncol (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, United Kingdom.

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(a) Clonogenic assays following 24 h treatment of RT112, RAD51KD and Ku80KD cells with increasing PAN concentrations. All experiments were performed at least three times. Error bars represent the mean and standard deviation (SD). (b) Quantification of γH2AX foci in DMSO- or PAN-treated cells, 24 h after treatment (see Supplementary Fig. 2 for confocal images). (c) Cell-cycle phase distributions in cells treated with increasing concentrations of PAN for 24 h. (d) Western blots from RT112 cells incubated with PAN for 24 h, showing downregulation of MRE11, NBS1 and RAD51 but not Ku70 or Ku80, with acetylation of H3K18 from 10 nM or greater PAN.
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f0005: (a) Clonogenic assays following 24 h treatment of RT112, RAD51KD and Ku80KD cells with increasing PAN concentrations. All experiments were performed at least three times. Error bars represent the mean and standard deviation (SD). (b) Quantification of γH2AX foci in DMSO- or PAN-treated cells, 24 h after treatment (see Supplementary Fig. 2 for confocal images). (c) Cell-cycle phase distributions in cells treated with increasing concentrations of PAN for 24 h. (d) Western blots from RT112 cells incubated with PAN for 24 h, showing downregulation of MRE11, NBS1 and RAD51 but not Ku70 or Ku80, with acetylation of H3K18 from 10 nM or greater PAN.

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).


Radiosensitisation of bladder cancer cells by panobinostat is modulated by Ku80 expression.

Groselj B, Kerr M, Kiltie AE - Radiother Oncol (2013)

(a) Clonogenic assays following 24 h treatment of RT112, RAD51KD and Ku80KD cells with increasing PAN concentrations. All experiments were performed at least three times. Error bars represent the mean and standard deviation (SD). (b) Quantification of γH2AX foci in DMSO- or PAN-treated cells, 24 h after treatment (see Supplementary Fig. 2 for confocal images). (c) Cell-cycle phase distributions in cells treated with increasing concentrations of PAN for 24 h. (d) Western blots from RT112 cells incubated with PAN for 24 h, showing downregulation of MRE11, NBS1 and RAD51 but not Ku70 or Ku80, with acetylation of H3K18 from 10 nM or greater PAN.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3824066&req=5

f0005: (a) Clonogenic assays following 24 h treatment of RT112, RAD51KD and Ku80KD cells with increasing PAN concentrations. All experiments were performed at least three times. Error bars represent the mean and standard deviation (SD). (b) Quantification of γH2AX foci in DMSO- or PAN-treated cells, 24 h after treatment (see Supplementary Fig. 2 for confocal images). (c) Cell-cycle phase distributions in cells treated with increasing concentrations of PAN for 24 h. (d) Western blots from RT112 cells incubated with PAN for 24 h, showing downregulation of MRE11, NBS1 and RAD51 but not Ku70 or Ku80, with acetylation of H3K18 from 10 nM or greater PAN.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Gray Institute for Radiation Oncology and Biology, Department of Oncology, University of Oxford, United Kingdom.

Show MeSH
Related in: MedlinePlus