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地锦草通过抑制肿瘤坏死因子α诱导的基质金属蛋白酶-9表达来抑制乳腺癌细胞的侵袭和转移。

Euphorbia humifusa Willd exerts inhibition of breast cancer cell invasion and metastasis through inhibition of TNFα-induced MMP-9 expression.

作者信息

Shin Soon Young, Kim Chang Gun, Jung You Jung, Jung Yearam, Jung Hyeryoung, Im Jihyun, Lim Yoongho, Lee Young Han

机构信息

Department of Biological Sciences, College of Biological Science and Biotechnology, Konkuk University, Seoul, Republic of Korea.

Cancer and Metabolism Institute, Konkuk University, Seoul, Republic of Korea.

出版信息

BMC Complement Altern Med. 2016 Oct 24;16(1):413. doi: 10.1186/s12906-016-1404-6.

DOI:10.1186/s12906-016-1404-6
PMID:27776550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5078950/
Abstract

BACKGROUND

Breast cancer is the most common type of malignancy in women worldwide. Euphorbia humifusa Willd (EuH) is a plant that is widely used as a traditional medicine. However, no systemic studies on the anti-cancer effects of EuH have been reported. The aim of this study is to evaluate the anti-metastatic effect of the EuH.

METHODS

Ethyl acetate fraction was prepared from EuH methanol extracts (EA/EuH). Inhibitory effect of EA/EuH on cell migration was determined using an in vitro scratch-wound healing assay. The anti-invasive activity was determined by in vitro three-dimensional spheroid culture system and in vivo syngenic experimental lung metastasis experiment. Gene expression profiles were analyzed by using RT-PCR, real-time PCR, and luciferase reporter assay systems.

RESULTS

Ethyl acetate fraction from the EuH extract (EA/EuH) inhibited the migration and invasive capabilities of highly metastatic MDA-MB-231 breast cancer cells and attenuated syngeneic lung metastasis of mouse 4 T1 breast cancer cells in vivo. Mechanistically, EA/EuH decreased tumor necrosis factor alpha (TNFα)-induced matrix metalloproteinase (MMP)-9 mRNA expression through the inhibition of NF-κB activity in MDA-MB-231 cells.

CONCLUSION

EuH may be beneficial in the prevention of invasion and metastasis of early stage breast cancer and can be served as an anti-metastatic agent or adjuvant therapy against metastatic breast cancer.

摘要

背景

乳腺癌是全球女性中最常见的恶性肿瘤类型。地锦草是一种被广泛用作传统药物的植物。然而,尚未有关于地锦草抗癌作用的系统性研究报道。本研究的目的是评估地锦草的抗转移作用。

方法

从地锦草甲醇提取物中制备乙酸乙酯馏分(EA/EuH)。使用体外划痕愈合试验测定EA/EuH对细胞迁移的抑制作用。通过体外三维球体培养系统和体内同基因实验性肺转移实验测定抗侵袭活性。使用逆转录聚合酶链反应(RT-PCR)、实时聚合酶链反应和荧光素酶报告基因检测系统分析基因表达谱。

结果

地锦草提取物中的乙酸乙酯馏分(EA/EuH)在体外抑制高转移性MDA-MB-231乳腺癌细胞的迁移和侵袭能力,并在体内减弱小鼠4T1乳腺癌细胞的同基因肺转移。机制上,EA/EuH通过抑制MDA-MB-231细胞中的核因子κB(NF-κB)活性,降低肿瘤坏死因子α(TNFα)诱导的基质金属蛋白酶(MMP)-9 mRNA表达。

结论

地锦草可能对预防早期乳腺癌的侵袭和转移有益,可作为抗转移剂或转移性乳腺癌的辅助治疗药物。

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