Decrease in MRE11 expression and function leads to increased sensitivity towards PARP inhibition in endometrial carcinoma cell lines.

<p>A, Efficiency of siRNAs at different time points after transfection shown by western blotting. B, Sensitivity assay (colorimetric with SRB): all cell lines were treated with PARP inhibitor (BMN673) in triplicates for 14 days. Survival is represented in percentage of the control (DMSO treated). Knock down of MRE11 with three different sets of siRNAs lead to an increased sensitivity towards PARP inhibition in the endometrial carcinoma cell lines HEC1A (8-fold increase, p<0.0001) and HEC-116 (6-fold increase, p = 0.0006). C, Cell lines were treated with the MRE11-inhibitor mirin at a final concentration of 30 µM in triplicates for 10 days. Survival was assessed by a colorimetric sensitivity assay (SRB) and is shown in percentage of the control (DMSO treated). Treatment with the MRE11-inhibitor mirin lead to increased sensitivity to PARP inhibition in both, HEC1A (2.6-fold increase, p = 0.001) and HEC-116 (17-fold increase, p<0.0001).