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顺铂与程序性细胞死亡蛋白5联合使用可通过促进细胞凋亡增强前列腺癌细胞的抗肿瘤活性。

Cisplatin in combination with programmed cell death protein 5 increases antitumor activity in prostate cancer cells by promoting apoptosis.

作者信息

Zhu Wenbin, Li Yang, Gao Lei

机构信息

Department of Urology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.

Department of Crushed Stones Center, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.

出版信息

Mol Med Rep. 2015 Jun;11(6):4561-6. doi: 10.3892/mmr.2015.3252. Epub 2015 Jan 26.

Abstract

Prostate cancer is the most common type of cancer affecting males. The aim of the present study was to investigate the antitumor effect of cisplatin in combination with programmed cell death protein 5 (Pdcd5) on Du145 prostate cancer cells and to elucidate the underlying mechanisms of action. An MTT cell viability assay was performed in order to determine the proliferation rate of Du145 cells. The results demonstrated that Du145 cells treated with cisplatin for 48 h had an IC50 value >200 µM; however, following transfection of Pdcd5 in combination with treatment with various concentrations of cisplatin, the proliferation rates of Du145 and PC3 prostate cancer cells were significantly decreased in a dose‑dependent manner, with IC50 values of 114.1 and 50.6 µM, respectively. Annexin V‑fluorescein isothiocyanate/propidium iodide dual labeling analyses demonstrated a significant increase in the apoptotic rate of Du145 cells following transfection of Pcdc5 in combination with cisplatin treatment. Furthermore, western blot analysis revealed a marked increase in activated caspase‑3 expression in Du145 cells as well as a decreased ratio of Bcl‑2/Bax. In conclusion, the results of the present study demonstrated that Pdcd5 increased the chemosensitivity of prostate cancer cells and decreased the toxicity of cisplatin via activation of the receptor‑associated apoptotic pathway; this may therefore indicate the combined use of cisplatin and Pdcd5 as a novel therapeutic strategy for the treatment of prostate cancer.

摘要

前列腺癌是影响男性的最常见癌症类型。本研究的目的是探讨顺铂与程序性细胞死亡蛋白5(Pdcd5)联合对Du145前列腺癌细胞的抗肿瘤作用,并阐明其潜在的作用机制。进行MTT细胞活力测定以确定Du145细胞的增殖率。结果表明,用顺铂处理48小时的Du145细胞的IC50值>200μM;然而,在转染Pdcd5并联合用不同浓度的顺铂处理后,Du145和PC3前列腺癌细胞的增殖率以剂量依赖性方式显著降低,IC50值分别为114.1和50.6μM。膜联蛋白V-异硫氰酸荧光素/碘化丙啶双标记分析表明,在转染Pcdc5并联合顺铂处理后,Du145细胞的凋亡率显著增加。此外,蛋白质印迹分析显示Du145细胞中活化的半胱天冬酶-3表达显著增加,以及Bcl-2/Bax比值降低。总之,本研究结果表明,Pdcd5通过激活受体相关的凋亡途径增加了前列腺癌细胞的化学敏感性并降低了顺铂的毒性;因此,这可能表明顺铂和Pdcd5联合使用作为治疗前列腺癌的一种新的治疗策略。

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