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小干扰 RNA 抑制 PARP1 增强多西他赛对人前列腺癌 PC3 细胞的活性。

Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells.

机构信息

Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, China.

出版信息

Biochem Biophys Res Commun. 2013 Dec 6;442(1-2):127-32. doi: 10.1016/j.bbrc.2013.11.027. Epub 2013 Nov 15.

Abstract

Though poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have benefits in combination with radiotherapy in prostate cancers, few is known about the exactly role and underlying mechanism of PARP1 in combination with chemotherapy agents. Here our data revealed that inhibition of PARP1 by small interfering RNA (siRNA) could enhance docetaxel's activity against PC3 cells, which is associated with an accelerate repression of EGF/Akt/FOXO1 signaling pathway. Our results provide a novel role of PARP1 in transcription regulation of EGFR/Akt/FOXO1 signaling pathway and indicate that PARP1 siRNA combined with docetaxel can be an innovative treatment strategy to potentially improve outcomes in CRPC patients.

摘要

尽管聚(ADP-核糖)聚合酶 1(PARP1)抑制剂与放射疗法联合应用于前列腺癌有一定的益处,但对于 PARP1 与化疗药物联合应用的确切作用和潜在机制知之甚少。我们的数据显示,小干扰 RNA(siRNA)抑制 PARP1 可以增强多西他赛对 PC3 细胞的活性,这与加速抑制 EGF/Akt/FOXO1 信号通路有关。我们的结果提供了 PARP1 在 EGFR/Akt/FOXO1 信号通路转录调控中的新作用,并表明 PARP1 siRNA 联合多西他赛可能是一种创新的治疗策略,有望改善 CRPC 患者的治疗效果。

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