Tumor Growth Inhibition by DNA Damage Response Modulators

All animal experiments were performed with the approval of Animal Care and Use Ethics Committee of Army Medical Center of PLA. (i) HeLa NC and HeLa shAPE1 cells (ii) HeLa WT cells (5 × 10⁶ in 100 ul medium with Matrigel) were injected subcutaneously in flank of 8 week-old male nude mice. Subcutaneous tumors were allowed to grow for 2 weeks before treatments. When palpable tumors were visible, mice of (i) were divided into four and (ii) were divided into seven groups (n = 7 in each group). Mice were received treatments for 9 days (Ku55933, 10 mg/kg, intraperitonially, daily; E3330, 40 mg/kg intraperitonially, daily; Inhibitor III, 20 mg/kg, intraperitonially, daily; IR, 5 Gy, every 2 days). Specifically, Mice were treated with (i) vehicle, Ku55933, IR, Ku55933 + IR (ii) vehicle, IR, E3330 + IR, Inhibitor III + IR, Ku55933 + IR, E3330 + Ku55933 + IR, and Inhibitor III + Ku55933 + IR. Unblinded tumor measurements were recorded once every 2 days and the volume as calculated by the formula: (width) 2 × length/3. The mice were euthanized in a gas canister with gradual fill carbon dioxide at the end of the treatment cycles and sacrificed. Weighed the tumor with electronic scale.