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

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...

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主要作者: Gonzalo Rodriguez-Berriguete (15056057) (author)
其他作者: Marco Ranzani (15056060) (author), Remko Prevo (15056063) (author), Rathi Puliyadi (15056066) (author), Nicole Machado (15056069) (author), Hannah R. Bolland (15056072) (author), Val Millar (15056075) (author), Daniel Ebner (15056078) (author), Marie Boursier (15056081) (author), Aurora Cerutti (15056084) (author), Alessandro Cicconi (15056087) (author), Alessandro Galbiati (15056090) (author), Diego Grande (15056093) (author), Vera Grinkevich (15056096) (author), Jayesh B. Majithiya (15056099) (author), Desiree Piscitello (15056102) (author), Eeson Rajendra (15056105) (author), Martin L. Stockley (15056108) (author), Simon J. Boulton (15056111) (author), Ester M. Hammond (15056114) (author), Robert A. Heald (15056117) (author), Graeme C.M. Smith (15056120) (author), Helen M.R. Robinson (15056123) (author), Geoff S. Higgins (15056126) (author)
出版: 2025
主题:
Cancer
Molecular and Cellular Biology
Therapeutic Research and Development
DNA Damage and Repair
DNA repair
Radiation Oncology
Molecular targets of radiation response
Small Molecule Agents
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总结:<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 G<sub>1</sub> 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>

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