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泽林酮通过下调 Wnt/β-连环蛋白通路抑制人前列腺癌的进展。

Zeylenone represses the progress of human prostate cancer by downregulating the Wnt/β‑catenin pathway.

机构信息

Department of Urology Surgery, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong 511518, P.R. China.

Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong 511518, P.R. China.

出版信息

Mol Med Rep. 2018 Dec;18(6):5572-5578. doi: 10.3892/mmr.2018.9564. Epub 2018 Oct 17.

DOI:10.3892/mmr.2018.9564
PMID:30365080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6236222/
Abstract

Prostate cancer (PCa) is one of the most common types of cancer in the urinary system in men. Zeylenone (Zey), a naturally occurring cyclohexene oxide, has an anticancer effect. In the present study, the role and potential mechanism of Zey in PCa were examined. The proliferative, invasive and migratory capacities of DU145 cells were analyzed using Cell Counting Kit‑8, transwell and wound healing assays, respectively. The expression levels of matrix metalloproteinase (MMP)‑2 and MMP‑9 were determined with an ELISA. Reverse transcription‑quantitative polymerase chain reaction and western blotting assays were performed to evaluate the expression levels of extracellular matrix, epithelial‑mesenchymal transition and Wnt/β‑catenin pathway‑associated factors. In the present study, it was observed that Zey not only suppressed the viability of DU145 cells; however, it additionally attenuated the invasive and migratory capacities of cells in a concentration‑dependent manner. Treatment of Zey decreased the expression levels of MMP‑2, MMP‑9 and fibronectin‑1; whereas, it increased tissue inhibitor of metalloproteinases‑1 and collagen‑1 expression levels. Additionally, the vimentin expression level was downregulated, however, the epithelial‑cadherin expression level was upregulated in cells treated with Zey. Furthermore, Zey decreased the expression levels of wnt5a, β‑catenin and cyclin D1. In conclusion, the present results demonstrated that Zey decreased the viability and metastasis of human PCa cells (DU145), via the Wnt/β‑catenin signaling pathway. Therefore, Zey may be applied as a novel drug for treating PCa in the future.

摘要

前列腺癌(PCa)是男性泌尿系统中最常见的癌症类型之一。泽仑诺(Zey)是一种天然存在的环己烯氧化物,具有抗癌作用。本研究旨在探究 Zey 在 PCa 中的作用及潜在机制。采用细胞计数试剂盒-8 检测、Transwell 检测和划痕愈合实验分别分析 DU145 细胞的增殖、侵袭和迁移能力。采用 ELISA 检测基质金属蛋白酶(MMP)-2 和 MMP-9 的表达水平。采用逆转录-定量聚合酶链反应和 Western blot 检测评估细胞外基质、上皮-间充质转化和 Wnt/β-连环蛋白通路相关因子的表达水平。本研究结果表明,Zey 不仅抑制 DU145 细胞的活力,而且还呈浓度依赖性地减弱细胞的侵袭和迁移能力。Zey 处理降低了 MMP-2、MMP-9 和纤连蛋白-1 的表达水平,而增加了组织金属蛋白酶抑制剂-1 和胶原-1 的表达水平。此外,Zey 下调了波形蛋白的表达水平,而上调了细胞中上皮钙黏蛋白的表达水平。此外,Zey 降低了 wnt5a、β-连环蛋白和细胞周期蛋白 D1 的表达水平。综上所述,本研究结果表明,Zey 通过 Wnt/β-连环蛋白信号通路降低了人 PCa 细胞(DU145)的活力和转移能力。因此,Zey 将来可能被应用于治疗 PCa 的新型药物。

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