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中国癌症防治杂志

中国癌症防治杂志 ›› 2014, Vol. 6 ›› Issue (4): 348-352.doi: 10.3969/j.issn.1674-5671.2014.04.06

• 基础研究 • 上一篇    下一篇

尼日菌素对前列腺癌DU145细胞Wnt/β-catenin信号传导的影响

  

  1. 福建省立医院干部特诊一科，福建医科大学省立临床医学院；上海交通大学医学院附属瑞金医院外科
  • 出版日期:2014-12-25 发布日期:2015-01-12
  • 通讯作者: 金润森 E-mail:jinrs_1985@eyou.com

Effects of nigericin on Wnt/β-catenin signaling in DU145 prostate cancer cells

  • Online:2014-12-25 Published:2015-01-12

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摘要： 目的 研究尼日菌素对前列腺癌DU145细胞的作用及其对Wnt/β-catenin信号传导的影响。方法 体外使用5 μmol/L、10 μmol/L、20 μmol/L的尼日菌素处理前列腺癌DU145细胞，同时以DMSO处理作为对照组。用细胞增殖-毒性检测试剂盒（CCK-8）检测尼日菌素对DU145细胞增殖活力的影响。以Transwell迁移侵袭实验检测药物对细胞的迁移侵袭能力的影响。用Western免疫印迹技术、免疫荧光及TOP/FOP-flash荧光报告试验检测尼日菌素对DU145细胞中β-catenin蛋白的表达及其下游靶基因c-myc及cyclin D1的表达以及对TCF/LEF 转录因子活性的影响。结果 尼日菌素对前列腺癌DU145细胞有明显的细胞毒性作用，可以抑制其侵袭和转移；尼日菌素可以降低DU145细胞中β-catenin蛋白的表达，从而阻断Wnt信号的传导，抑制下游转录因子的活性、降低靶基因的表达水平。结论 尼日菌素可显著抑制前列腺癌细胞的侵袭与转移，可能与其抑制Wnt/β-catenin信号传导相关。

关键词: 前列腺肿瘤, 尼日菌素, 前列腺癌细胞, Wnt/β-catenin信号传导, 侵袭, 转移

Abstract: Objective To evaluate the effect of nigericin on DU145 prostatecancer cells and explore its influence on Wnt/β-catenin signaling. Methods The human prostate cancer cell line DU145 was treated with 5，10 or 20 μmol/L nigericin or with DMSO as a control. Cultures were assessed for viability using the Cell Counting Kit-8，and for migration and invasion ability using transwell assays. The expression of β-catenin and its downstream target genes was analyzed using Western blotting， immunofluorescence and TOP/FOP-flash reporter assays. Results Nigericin showed significant toxicity towards DU145 cells and markedly inhibited their migratory and invasive abilities. The drug also reduced the expression of β-catenin，suppressing the Wnt/β-catenin pathway and down-regulating downstream target genes. Conclusion These findings suggest that nigericin significantly inhibits invasion and metastasis of DU145 prostate cancer cells in vitro， and that the drug likely exerts these effects by suppressing Wnt/β-catenin signaling.

Key words: Prostate neoplasm, Nigericin, Prostate cancer cell, Wnt/β-catenin signaling, Invasion, Migration