ArticleInternational urology and nephrology2026
The MTH1 inhibitor TH287 sensitized Castration-Resistant Prostate Cancer cells to ionizing radiation therapy.
Article in International urology and nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo determine whether the MutT Homolog 1 (MTH1) inhibition could increase the sensitivity of Castration-Resistant Prostate Cancer (CRPC) cells to Radiotherapy (RT), as well as to determine the appropriate application time of the MTH1 inhibitor and RT to achieve optimal radiosensitizing effects.
methodsPC-3 and DU-145 cells were selected as the model cell lines for CRPC. After 24 h of incubation, the cells were treated with various doses of the MTH1 inhibitor TH287 for 72 h, during which they were subjected to Ionizing Radiation (IR) treatment at 12, 24, and 48 h after the initial drug treatment. Cell survival was evaluated through the Cell Counting Kit 8 (CCK-8) assay. Apoptotic induction and cell cycle progression were evaluated through Western Blotting (WB) and flow cytometry analyses.
resultsThe CCK-8 assay revealed that the TH287 + IR combination therapy significantly inhibited PC3 and DU145 cell survival, with the most potent effects observed in the combined IR administration at 12 h (P < 0.05). Furthermore, Annexin-V/PI (Propidium Iodide) dual staining revealed that the TH287 + IR combination treatment induced apoptotic tumor cell death more effectively than either treatment alone (P < 0.05). Moreover, WB analysis revealed that the TH287 + IR combination therapy significantly altered caspase-3 expression, indicating DNA damage induction and modulation of various cell cycle-related proteins. Moreover, flow cytometry analysis revealed that the TH287 + IR treatment caused significant G2/S-phase arrest in prostate cancer cells (P < 0.05).
conclusionOverall, TH287 exhibited potent radiosensitization effects for CRPC treatment, effectively killing tumor cells when administered alongside IR at 12 h after the initial drug treatment.
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