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葛根素通过阻断 NF-κB 和 Erk 通路抑制 LPS 诱导的乳腺癌细胞迁移、侵袭和黏附。

Puerarin suppresses LPS-induced breast cancer cell migration, invasion and adhesion by blockage NF-κB and Erk pathway.

机构信息

Inspection Center, Huai'an No 4 People's Hospital, Huai'an 223002, China.

Department of Laboratory, Nanjing Maternity and Child Health Care Hospital, Nanjing 210000, China.

出版信息

Biomed Pharmacother. 2017 Aug;92:429-436. doi: 10.1016/j.biopha.2017.05.102. Epub 2017 May 27.

DOI:10.1016/j.biopha.2017.05.102
PMID:28558356
Abstract

BACKGROUND

Chronic inflammation is a major risk factor for the development and metastatic progression of breast cancer. Puerarin has long been used as traditional Chinese medicine, which possesses manifold physiological activities, including anti-inflammation and anti-cancer activities. However, its anti-cancer metastasis activity in breast cancer cell inflammation-mediated have not been studied.

METHODS

Cell viability was detected with Cell Counting Kit (CCK)-8. Transwell migration and invasion assay were performed to evaluate cell migration and invasion, respectively. Enzyme-linked immunosorbent assay (ELISA) was conducted to analysis the expression of inflammatory factor. In addition, mRNA and protein levels of related cytokines were determined by qRT- PCR assay and western blot analysis, respectively.

RESULTS

In this study, puerarin significantly inhibited lipopolysaccharide (LPS)-induced MCF-7 and MDA-MB-231 cell migration, invasion and adhesion. The mRNA and protein levels revealed that puerarin treatment effectively negated the expression of CCR7, CXCR4, MMP-2, MMP-9, ICAM and VCAM in LPS- activated MCF-7 and MDA-MB-231 cells. Further, the expression of inflammatory factor TNF-α and IL-6 in cell culture supernatant remarkably reduced. Finally, the result indicated that puerarin abrogated the NF-κB activation in breast cancer cells stimulated by LPS, which is mediated through inhibition of phosphorylation of p65 and IκBα. Also, puerarin inhibited phosphorylation of Erk in breast cancer cells LPS-induced.

CONCLUSIONS

This present study revealed that puerarin might be a novel therapeutic drug for breast cancer treatment.

摘要

背景

慢性炎症是乳腺癌发生和转移进展的一个主要危险因素。葛根素作为传统中药已被使用了很长时间,它具有多种生理活性,包括抗炎和抗癌活性。然而,其在乳腺癌细胞炎症介导中的抗癌转移活性尚未得到研究。

方法

用细胞计数试剂盒(CCK)-8 检测细胞活力。用 Transwell 迁移和侵袭实验分别评估细胞迁移和侵袭。酶联免疫吸附试验(ELISA)用于分析炎症因子的表达。此外,通过 qRT-PCR 分析和 Western blot 分析分别测定相关细胞因子的 mRNA 和蛋白水平。

结果

在这项研究中,葛根素显著抑制脂多糖(LPS)诱导的 MCF-7 和 MDA-MB-231 细胞迁移、侵袭和黏附。mRNA 和蛋白水平表明,葛根素处理有效否定了 LPS 激活的 MCF-7 和 MDA-MB-231 细胞中 CCR7、CXCR4、MMP-2、MMP-9、ICAM 和 VCAM 的表达。此外,细胞培养上清液中炎症因子 TNF-α和 IL-6 的表达显著降低。最后,结果表明,葛根素通过抑制 p65 和 IκBα 的磷酸化,阻断 LPS 刺激的乳腺癌细胞中 NF-κB 的激活。此外,葛根素抑制了 LPS 诱导的乳腺癌细胞中 Erk 的磷酸化。

结论

本研究表明,葛根素可能是一种治疗乳腺癌的新型治疗药物。

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