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紫草素通过Toll样受体2/核因子-κB途径抑制人胃癌细胞系MGC-803的细胞活力、黏附、侵袭和迁移。

Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway.

作者信息

Liu Ji Ping, Liu Dan, Gu Jun Fei, Zhu Mao Mao, Cui Li

机构信息

Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.

Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang, China.

出版信息

J Pharm Pharmacol. 2015 Aug;67(8):1143-55. doi: 10.1111/jphp.12402. Epub 2015 Apr 16.

Abstract

OBJECTIVES

Shikonin is an active naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon. This study was designed to explore the inhibition of Shikonin on cell viability, adhesion, migration and invasion ability of gastric cancer (GC) and its possible mechanism.

METHODS

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for cell viability and adhesion ability of MGC-803 cells. Cell scratch repair experiments were conducted for the determination of migration ability while transwell assay for cell invasion ability. Western blot analysis and real-time polymerase chain reaction assay were used for the detection of protein and mRNA expressions.

KEY FINDINGS

Fifty per cent inhibitory concentration of Shikonin on MGC-803 cells was 1.854 μm. Shikonin (1 μm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells. Interestingly, Shikonin in the presence or absence of anti-Toll-like receptor 2 (TLR2) antibody (2 μg) and nuclear factor-kappa B (NF-κB) inhibitor MG-132 (10 μm) could decrease these ability of MGC-803 cells markedly, as well as the expression levels of matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB. In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone.

CONCLUSIONS

The results indicated that Shikonin could suppress the cell viability, adhesion, invasion and migratory ability of MGC-803 cells through TLR2- or NF-κB-mediated pathway. Our findings provide novel information for the treatment of Shikonin on GC.

摘要

目的

紫草素是从紫草根部分离得到的一种活性萘醌色素。本研究旨在探讨紫草素对胃癌(GC)细胞活力、黏附、迁移和侵袭能力的抑制作用及其可能机制。

方法

采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测MGC-803细胞的活力和黏附能力。进行细胞划痕修复实验以测定迁移能力,采用Transwell实验检测细胞侵袭能力。利用蛋白质免疫印迹分析和实时聚合酶链反应检测蛋白质和mRNA表达。

主要发现

紫草素对MGC-803细胞的半数抑制浓度为1.854μm。紫草素(1μm)显著抑制MGC-803细胞的黏附、侵袭和迁移能力。有趣的是,无论有无抗Toll样受体2(TLR2)抗体(2μg)和核因子-κB(NF-κB)抑制剂MG-132(10μm),紫草素均可显著降低MGC-803细胞的这些能力,以及基质金属蛋白酶(MMP)-2、MMP-7、TLR2和p65 NF-κB的表达水平。此外,紫草素与抗TLR2/MG-132共同孵育的活性明显强于单独使用抗TLR2或MG-132。

结论

结果表明,紫草素可通过TLR2或NF-κB介导的途径抑制MGC-803细胞的活力、黏附、侵袭和迁移能力。我们的研究结果为紫草素治疗胃癌提供了新的信息。

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