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- W4361948678 abstract "<div>Abstract<p><b>Purpose:</b> The inhibitor of apoptosis proteins (IAP) are overexpressed in hormone-refractory prostate cancer, rendering the cancer cells resistant to radiation. This study aims to investigate the radiosensitizing effect of small-molecule IAP inhibitor both <i>in vitro</i> and <i>in vivo</i> in androgen-independent prostate cancer and the possible mechanism of radiosensitization.</p><p><b>Experimental Design:</b> Radiosensitization of SH-130 in human prostate cancer DU-145 cells was determined by clonogenic survival assay. Combination effect of SH-130 and ionizing radiation was evaluated by apoptosis assays. Pull-down and immunoprecipitation assays were employed to investigate the interaction between SH-130 and IAPs. DU-145 xenografts in nude mice were treated with SH-130, radiation, or combination, and tumor suppression effect was determined by caliper measurement or bioluminescence imaging. Nuclear factor-κB activation was detected by luciferase reporter assay and quantitative real-time PCR.</p><p><b>Results:</b> SH-130 potently enhanced radiation-induced caspase activation and apoptosis in DU-145 cells. Both X-linked IAP and cIAP-1 can be pulled down by SH-130 but not by inactive SH-123. Moreover, SH-130 interrupted interaction between X-linked IAP/cIAP-1 and Smac. In a nude mouse xenograft model, SH-130 potently sensitized the DU-145 tumors to X-ray radiation without increasing systemic toxicity. The combination therapy suppressed tumor growth more significantly than either treatment alone, with over 80% of complete tumor regression. Furthermore, SH-130 partially blocked tumor necrosis factor-α- and radiation-induced nuclear factor-κB activation in DU-145 cells.</p><p><b>Conclusions:</b> Our results show that small-molecule inhibitors of IAPs can overcome apoptosis resistance and radiosensitize human prostate cancer with high levels of IAPs. Molecular modulation of IAPs may improve the outcome of prostate cancer radiotherapy.</p></div>" @default.
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- W4361948678 date "2023-03-31" @default.
- W4361948678 modified "2023-10-18" @default.
- W4361948678 title "Data from Molecularly Targeted Radiosensitization of Human Prostate Cancer by Modulating Inhibitor of Apoptosis" @default.
- W4361948678 doi "https://doi.org/10.1158/1078-0432.c.6516952.v1" @default.
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