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组蛋白去乙酰化酶抑制剂CG-745增强前列腺癌细胞的放射敏感性。

The histone deacetylase inhibitor CG-745 enhances the radiosensitivity of prostate cancer cells.

作者信息

Wu Bin, Liao Shao-Guang

机构信息

Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, China.

Department of Radiation Oncology, Huangyan Hospital of Wenzhou Medical University, Taizhou First People's Hospital, China.

出版信息

J Int Med Res. 2025 Sep;53(9):3000605251371562. doi: 10.1177/03000605251371562. Epub 2025 Sep 2.

DOI:10.1177/03000605251371562
PMID:40891806
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12409009/
Abstract

ObjectiveTo investigate the possible correlation between histone deacetylase inhibition and radiosensitivity in PC-3 prostate cancer cells and to explore the possible mechanism involved.MethodsPC-3 prostate cancer cells were treated with 0.40 μM CG-745 alone, radiation alone, or 0.40 μM CG-745 in combination with radiation. A CCK-8 kit was used to measure the proliferation of PC-3 cells. The colony formation assay was used to determine cell reproductive survival. Immunofluorescence analysis was used to detect the location of phosphorylated H2AX foci. Apoptosis and cell cycle distribution of PC-3 cells were assessed via flow cytometry analysis.ResultsCG-745 enhances the repressive effect of irradiation on PC-3 cell growth, as shown by the CCK-8 assay and colony formation assay. Compared with CG-745 or radiation alone, CG-745 combined with radiation significantly increased phosphorylated H2AX foci formation. The combination of CG-745 and radiation significantly increased the percentage of cells in the S phase and decreased percentage of cells in the G2 and G1 phases compared with treatment with CG-745 alone or radiation alone. Flow cytometry analysis showed that CG-745 promoted the PC-3 cell apoptosis induced by radiation.ConclusionsThe histone deacetylase inhibitor CG-745 enhanced radiation-induced DNA damage, cell cycle arrest, and cell apoptosis, thus increasing the radiosensitivity of PC-3 prostate cancer cells to X-ray irradiation.

摘要

目的

研究组蛋白去乙酰化酶抑制与PC-3前列腺癌细胞放射敏感性之间的可能相关性,并探讨其中涉及的可能机制。

方法

PC-3前列腺癌细胞分别用0.40 μM CG-745单独处理、单独放疗或0.40 μM CG-745与放疗联合处理。使用CCK-8试剂盒检测PC-3细胞的增殖情况。采用集落形成试验确定细胞的增殖存活情况。免疫荧光分析用于检测磷酸化H2AX焦点的位置。通过流式细胞术分析评估PC-3细胞的凋亡和细胞周期分布。

结果

CCK-8试验和集落形成试验表明,CG-745增强了辐射对PC-3细胞生长的抑制作用。与单独使用CG-745或放疗相比,CG-745与放疗联合显著增加了磷酸化H2AX焦点的形成。与单独使用CG-745或放疗相比,CG-745与放疗联合显著增加了S期细胞的百分比,降低了G2期和G1期细胞的百分比。流式细胞术分析表明,CG-745促进了辐射诱导的PC-3细胞凋亡。

结论

组蛋白去乙酰化酶抑制剂CG-745增强了辐射诱导的DNA损伤、细胞周期阻滞和细胞凋亡,从而增加了PC-3前列腺癌细胞对X射线照射的放射敏感性。

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