Targeting HR via CDK inhibition resensitizes recurrent cultures to temozolomide (TMZ). Targeting HR via CDK inhibition resensitizes recurrent cultures.

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Targeting HR via CDK inhibition resensitizes recurrent cultures to temozolomide (TMZ). Targeting HR via CDK inhibition resensitizes recurrent cultures to temozolomide (TMZ). A, recurrent cultures (419 and 481) were treated with 10 μmol/L TMZ for 48 hours followed by addition of either DMSO or CDK inhibitors (AZD5438 or roscovitine). Cells were fixed at the indicated times post-TMZ treatment, immunofluorescence-stained for 53BP1 foci (red), and imaged at 40× magnification. Nuclei are stained with DAPI (blue). Representative images are shown. Rates of repair of TMZ-induced DSBs were determined by scoring 53BP1 foci. Average number of 53BP1 foci per nucleus (y-axis) is plotted against the corresponding time posttreatment (x-axis). Error bars, SEM. ****, P < 0.0001 (TMZ + DMSO vs. TMZ + AZD or TMZ + roscovitine at 48 hours). B, TMZ sensitivities of the recurrent cultures (419 and 481) treated with DMSO or with CDK inhibitors (AZD5438 or roscovitine) were assessed by colony formation assays. The fraction of surviving colonies (y-axis) is plotted against the corresponding TMZ dose (x-axis). Error bars, SD. *, P = 0.0109; **, P = 0.0019; ***, P = 0.0006. Carlos Rodrigo Gil del Alcazar et al. Mol Cancer Res 2016;14:928-940 ©2016 by American Association for Cancer Research