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聚(ADP-核糖)聚合酶(PARP)抑制使子宫内膜癌细胞对紫杉醇诱导的凋亡敏感。

PARP inhibition sensitizes endometrial cancer cells to paclitaxel-induced apoptosis.

作者信息

Dinkic Christine, Jahn Friederike, Zygmunt Marek, Schuetz Florian, Rom Joachim, Sohn Christof, Fluhr Herbert

机构信息

Department of Gynecology and Obstetrics, Heidelberg University Hospital, D-69120 Heidelberg, Germany.

Department of Gynecology and Obstetrics, Greifswald University Hospital, D-17475 Greifswald, Germany.

出版信息

Oncol Lett. 2017 Apr;13(4):2847-2851. doi: 10.3892/ol.2017.5795. Epub 2017 Mar 1.

Abstract

PARP inhibitors are used in the treatment of gynecological malignancies and it has been demonstrated in preclinical studies that PARP inhibition sensitizes cancer cells to cytotoxic agents. In the present study, PARP expression was detected in different endometrial cancer cell lines by western blot analysis, and PARP activity was measured using an enzymatic assay. In addition, the endometrial cancer cell lines were treated with paclitaxel or carboplatin in combination with the PARP inhibitor PJ34 prior to a cell viability assay and apoptotic nuclei measurement. PARP protein was detected in all four cell lines examined, although its activity varied between the cell lines. Treatment with PJ34 in combination with paclitaxel decreased endometrial cancer cell viability compared with treatment with paclitaxel alone. These results indicate that the inhibition of PARP with PJ34 sensitizes endometrial cancer cells to cytotoxic treatment with paclitaxel.

摘要

聚(ADP - 核糖)聚合酶(PARP)抑制剂用于治疗妇科恶性肿瘤,临床前研究已证明PARP抑制可使癌细胞对细胞毒性药物敏感。在本研究中,通过蛋白质印迹分析在不同的子宫内膜癌细胞系中检测PARP表达,并使用酶促测定法测量PARP活性。此外,在进行细胞活力测定和凋亡细胞核测量之前,将子宫内膜癌细胞系用紫杉醇或卡铂与PARP抑制剂PJ34联合处理。在所检测的所有四种细胞系中均检测到PARP蛋白,尽管其活性在各细胞系之间有所不同。与单独使用紫杉醇治疗相比,PJ34与紫杉醇联合治疗降低了子宫内膜癌细胞的活力。这些结果表明,用PJ34抑制PARP可使子宫内膜癌细胞对紫杉醇细胞毒性治疗敏感。

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