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凋亡途径在二十二碳六烯酸诱导的前列腺癌获益中的作用:使用RT Profile PCR阵列系统进行的途径聚焦基因表达分析。

Involvement of apoptotic pathways in docosahexaenoic acid-induced benefit in prostate cancer: Pathway-focused gene expression analysis using RT Profile PCR Array System.

作者信息

Sun Yanan, Jia Xiaopeng, Hou Lianguo, Liu Xing, Gao Qiang

机构信息

Department of Obstetrics and Gynecology, Bethune International Peace Hospital of the People's Liberation Army, Shijiazhuang, 050082, China.

Department of Urology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China.

出版信息

Lipids Health Dis. 2017 Mar 23;16(1):59. doi: 10.1186/s12944-017-0442-5.

DOI:10.1186/s12944-017-0442-5
PMID:28330470
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5363041/
Abstract

BACKGROUND

Present study aimed to better understand the potential apoptotic pathways that involved in docosahexaenoic acid (DHA)-induced apoptosis of prostate cancer cells.

METHODS

Human prostate cancer DU145 cells were treated with different concentrations of fish oil, omega-3 PUFA (DHA, and Eicosapentaenoic acid, EPA), or omega-6 PUFA (Arachidonic acid, AA). Cell viability and apoptosis were evaluated by MTT assay and Hoechst staining. Pathway-focused gene expression profiling of DU145 cells was analyzed with the RT Profile PCR Array System. The results were verified by real time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

AA exposure showed no obvious effect on viability of DU145 cells. However, exposure with fish oil, EPA, or DHA for 24 h significantly affected cell viability. The growth inhibition of DHA was more pronounced than that of EPA and showed a time-dependent increase. DHA exposure caused typical apoptotic characteristics. Ten genes were more expressed, while 5 genes were less expressed following DHA exposure. RT-qPCR confirmed the time dependent effect of DHA on the expression of these differentially expressed genes. KEGG pathway analysis showed that DHA may induce the apoptosis of cancer cells preferentially through mediating P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways.

CONCLUSION

Our study demonstrated the beneficial action of DHA on human prostate carcinoma cell line DU145. The pro-apoptotic effect of DHA on DU145 cells may involve mediation various pathways, especially P53, MAPK, TNF, PI3K/AKT, and NF-κB signaling pathways. Molecular mechanisms of DHA on apoptosis of cancer cells still need to be further clarified.

摘要

背景

本研究旨在更好地了解二十二碳六烯酸(DHA)诱导前列腺癌细胞凋亡所涉及的潜在凋亡途径。

方法

用不同浓度的鱼油、ω-3多不饱和脂肪酸(DHA和二十碳五烯酸,EPA)或ω-6多不饱和脂肪酸(花生四烯酸,AA)处理人前列腺癌DU145细胞。通过MTT法和Hoechst染色评估细胞活力和凋亡情况。用RT Profile PCR Array System分析DU145细胞的通路聚焦基因表达谱。结果通过实时定量聚合酶链反应(RT-qPCR)进行验证。

结果

AA处理对DU145细胞活力无明显影响。然而,用鱼油、EPA或DHA处理24小时显著影响细胞活力。DHA的生长抑制作用比EPA更明显,且呈时间依赖性增加。DHA处理导致典型的凋亡特征。DHA处理后,10个基因表达上调,5个基因表达下调。RT-qPCR证实了DHA对这些差异表达基因表达的时间依赖性影响。KEGG通路分析表明,DHA可能通过介导P53、MAPK、TNF、PI3K/AKT和NF-κB信号通路优先诱导癌细胞凋亡。

结论

我们的研究证明了DHA对人前列腺癌细胞系DU145的有益作用。DHA对DU145细胞的促凋亡作用可能涉及多种途径的介导,尤其是P53、MAPK、TNF、PI3K/AKT和NF-κB信号通路。DHA诱导癌细胞凋亡的分子机制仍需进一步阐明。

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