Targeting proteins of the alt-NHEJ pathway sensitizes cells toward cytotoxic agents. (A) CCRF-HSB2 cells were treated with either (left) cytarabine or (center) daunorubicin in combination with the PARP inhibitor NU1025 (10 mM) or vehicle (dimethylsulfoxide). (Right) U-937 cells were treated with daunorubicin in combination with NU1025 (10 mM) or vehicle (dimethylsulfoxide). After 48 hours, the percentage of sub-G1 cells was determined by flow cytometry. Data represent the mean values ± SD of 3 independent experiments (*P < .05, Student t test). (B) Nomo-1 cells infected with nonsilencing miR-shRNA or KRAS miR-shRNA were treated with daunorubicin (60 nM) in combination with NU1025 (10 mM) in the presence or absence of doxycycline. (C) Nomo-1 cells either expressing tetracycline-controlled transcriptional activation (tet-on–inducible) miR-shRNA targeting Lig3α or nonsilencing miR-shRNA were treated with 1 µg/mL doxycyclin. Immunoblot analysis was performed using an anti-Lig3α antibody. To control equal loading, the blot was stripped and reprobed with anti–glyceraldehyde-3-phosphate dehydrogenase (GAPDH). (D) miR-shRNA expressing Nomo-1 cells were treated with either (upper) daunorubicin (DNR) or (lower) VP-16. After 72 (DNR) or 48 hours (VP-16), the percentage of sub-G1 cells was determined by flow cytometry. Data represent the mean values of 3 independent experiments. Error bars correspond to SD (**P < .01, ***P < .001, Student t test).