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通过橄榄苦苷同时下调 miR-21 和 miR-155 以预防和治疗乳腺癌。

Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy.

机构信息

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

J Cell Biochem. 2018 Sep;119(9):7151-7165. doi: 10.1002/jcb.26754. Epub 2018 Jun 15.

Abstract

Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.

摘要

乳腺癌(BC)是全球女性癌症死亡的主要原因。最近已经证明,miRNAs 在 BC 的发展中起着关键作用。通过调节 miRNAs 来利用天然药物控制癌症具有广阔的前景。橄榄苦苷是一种具有抗肿瘤特性的天然多酚类药物,在人类中具有良好的耐受性。本研究旨在通过调节乳腺癌细胞中的主致癌 miRNAs(miR-21 和 miR-155)来确定橄榄苦苷的治疗效果。本研究首次将 miRNA 与橄榄苦苷作为 BC 中的一种机制联系起来。用和不用橄榄苦苷对 MCF-7 细胞进行了测试,并检测了细胞活力、细胞凋亡和细胞迁移。通过 qRT-PCR 评估了橄榄苦苷对 miR-21 和 miR-155 表达的影响。结果发现,橄榄苦苷在人 MCF7 BC 细胞系中以剂量依赖性方式诱导细胞凋亡并减缓细胞迁移和侵袭。结果表明,橄榄苦苷随时间以剂量依赖性方式显著降低了两种 miR-21 和 miR-155 的表达。这些结果表明,橄榄苦苷是 BC 的一种潜在的治疗和预防剂。橄榄苦苷通过调节肿瘤抑制基因的表达发挥抗癌作用,而这些基因是致癌 miRNAs 的靶标。

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