Figure 1 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models

<p>The Polθ inhibitor ART558 radiosensitizes tumor cells. <b>A</b> and <b>B,</b> Clonogenic survival of HCT116, H460, and T24 cells treated with ART558 and/or IR. <b>A,</b> Plating efficiency for unirradiated cells. <b>B,</b> Surviving fractions as a function of the irradiation dose. Representative wells for 0 Gy and 6 Gy ± 1 μmol/L ART558 are shown for each cell line. <b>C,</b> Clonogenic survival of U2OS WT and Polθ KO cells treated with 3 μmol/L ART558 and 6 Gy IR. Bar graphs show the surviving fraction at 6 Gy. The Western blot insets confirm the lack of Polθ expression in the U2OS Polθ KO cells. <b>D,</b> Clonogenic survival of HCT116 and H460 cells transfected with either a control, nontargeting siRNA (siNT) or an siRNA targeted against <i>POLQ</i> (si<i>POLQ</i>) and treated with 3 μmol/L ART558 and 6 Gy IR. Bar graphs show the surviving fraction at 6 Gy. Western blots show Polθ expression at the time of irradiation. <b>E,</b> Clonogenic survival of H460 and HCT116 treated with 3 μmol/L ART558 and 5×2 Gy (2 Gy once per day for 1 to 5 days). <b>F</b> and <b>G,</b> Clonogenic survival following irradiation and treatment with 3 μmol/L ART558 of synchronized HeLa cells. <b>F,</b> Representative histograms showing the cell-cycle distribution at the time of IR (synchronized in G₁ by DT block or after 6 hours release from DT block, compared with asynchronous cultures). <b>G,</b> Degree of radiosensitization estimated by the ratio between the surviving fraction of DMSO- and ART558-treated cells after IR (SF DMSO / SF ART558). Data correspond to average ± SD from three independent experiments (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ****, <i>P</i> < 0.0001).</p>