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聚(ADP-核糖)聚合酶抑制剂鲁卡帕尼抑制增殖,并作为宫颈癌的有效放射增敏剂。

The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer.

机构信息

Jiangnan University, Jiangsu Wuxi, 214000, China.

Affilited Hospital of Jiangnan University, Huihe Road No.200, Wuxi, 214062, Jiangsu Province, China.

出版信息

Invest New Drugs. 2019 Feb;37(1):65-75. doi: 10.1007/s10637-018-0616-7. Epub 2018 Jun 6.

DOI:10.1007/s10637-018-0616-7
PMID:29872938
Abstract

Objectives Our goal was to investigate the effects of rucaparib on the proliferation of cervical cancer cells and sensitivity to radiotherapy. Methods We used the human cervical cancer cell lines Hela and Siha and evaluated their viability and activity using various methods. Cellular proliferation was assessed by CCK-8 and clonogenic assays after treatment with rucaparib. Cell cycle analysis was performed using propidium iodide staining. Western immunoblotting analysis was used to detect the expression of cyclin D1 and CDK4. Immunofluorescence staining assay was performed to detect the expression of the DNA injury marker ץ-H2AX after treatment with rucaparib and radiotherapy. Animal experiments were also performed to evaluate tumor size after treatment with rucaparib. Immunohistochemistry was performed to analyze the expression of Ki-67. Results Rucaparib suppressed proliferation, induced G2/M phase arrest, and reduced the expression of cyclin D1 and CDK4 in cervical cancer cells. When rucaparib was combined with radiotherapy in cervical cancer cells, clone formation decreased significantly and G2/M phase arrest was accentuated. The expression of the DNA-damage marker ץ-H2AX was increased significantly, and rucaparib suppressed tumor growth in vivo. Conclusions Rucaparib exerts significant anti-proliferative effects and can serve as an effective radiosensitizer in cervical cancer, suggesting its candidacy in cervical cancer treatment and worthiness for further investigation.

摘要

目的

研究芦卡帕利对宫颈癌增殖和放疗敏感性的影响。

方法

采用人宫颈癌 Hela 和 Siha 细胞系,用多种方法评估其活力和活性。用 CCK-8 和集落形成实验检测芦卡帕利处理后细胞的增殖。用碘化丙啶染色进行细胞周期分析。用 Western 免疫印迹分析检测芦卡帕利和放疗后细胞周期蛋白 D1 和 CDK4 的表达。用免疫荧光染色实验检测芦卡帕利和放疗后 DNA 损伤标志物 γ-H2AX 的表达。还进行了动物实验以评估芦卡帕利治疗后的肿瘤大小。用免疫组化分析 Ki-67 的表达。

结果

芦卡帕利抑制宫颈癌增殖,诱导 G2/M 期阻滞,并降低细胞周期蛋白 D1 和 CDK4 的表达。当芦卡帕利与宫颈癌细胞中的放疗联合使用时,克隆形成明显减少,G2/M 期阻滞加剧。DNA 损伤标志物 γ-H2AX 的表达显著增加,芦卡帕利在体内抑制肿瘤生长。

结论

芦卡帕利具有显著的抗增殖作用,可作为宫颈癌的有效增敏剂,提示其在宫颈癌治疗中的应用价值,值得进一步研究。

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