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丹酚酸 A 通过 ERK 信号通路抑制 MMP-2 的表达并抑制人鼻咽癌细胞的侵袭。

Salvianolic acid A suppresses MMP-2 expression and restrains cancer cell invasion through ERK signaling in human nasopharyngeal carcinoma.

机构信息

School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.

School of Medical Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan.

出版信息

J Ethnopharmacol. 2020 Apr 24;252:112601. doi: 10.1016/j.jep.2020.112601. Epub 2020 Jan 22.

DOI:10.1016/j.jep.2020.112601
PMID:31981746
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Salvia miltiorrhiza Bunge, as known as Danshen, has used for the prevention and treatment of cardiovascular diseases clinically and anti-cancer activities. Salvianolic acid A (SAA), one of the most abundant ingredients, hydrophilic derivatives of Salvia miltiorrhiza Bunge, exerts a variety of pharmacological actions, such as anti-oxidative, anti-inflammatory and anti-cancer activities. However, the impact of SAA on nasopharyngeal carcinoma (NPC) invasion and metastasis remains unexplored.

AIM OF THE STUDY

To investigate the potential of SAA to prevent migration and invasion on NPC cell.

MATERIALS AND METHODS

MTT assay and Boyden chamber assay were performed to determine cell proliferation, migration and invasion abilities, respectively. The activity and protein expression of matrix metalloproteinase-2 (MMP-2) were determined by gelatin zymography and western blotting.

RESULTS

Here, we showed that SAA considerably suppressed the migrative and invasive activity of human NPC cells but not rendered cytotoxicity. In SAA-treated NPC cells, the activity and expression of matrix metalloproteinase-2 (MMP-2), a key regulator of cancer cell invasion, were reduced. Additionally, the presence of high concentrations of SAA dramatically abolished the activation of focal adhesion kinase (FAK) and moderately inhibited the phosphorylation of Src and ERK in NPC cells.

CONCLUSIONS

Our results demonstrated that SAA inhibited the migration and invasion of NPC cells, accompanied by downregulation of MMP-2 and inactivation of FAK, Src, and ERK pathways. These findings indicate a usefulness of SAA on restraining NPC invasion and metastasis.

摘要

草药学相关性

丹参作为一种传统中药,在临床上已被用于预防和治疗心血管疾病以及抗癌。丹酚酸 A(SAA)是丹参中含量最丰富的成分之一,其亲水衍生物具有多种药理作用,如抗氧化、抗炎和抗癌作用。然而,SAA 对鼻咽癌(NPC)侵袭和转移的影响尚未得到研究。

研究目的

研究 SAA 对预防 NPC 细胞迁移和侵袭的潜力。

材料与方法

采用 MTT 法和 Boyden 室法分别测定细胞增殖、迁移和侵袭能力,明胶酶谱法和 Western blot 法测定基质金属蛋白酶-2(MMP-2)的活性和蛋白表达。

结果

本研究表明,SAA 能显著抑制人 NPC 细胞的迁移和侵袭活性,但不具有细胞毒性。在 SAA 处理的 NPC 细胞中,基质金属蛋白酶-2(MMP-2)的活性和表达,作为癌细胞侵袭的关键调节因子,被下调。此外,高浓度 SAA 的存在可显著抑制 NPC 细胞中粘着斑激酶(FAK)的激活,并适度抑制 Src 和 ERK 的磷酸化。

结论

我们的研究结果表明,SAA 可抑制 NPC 细胞的迁移和侵袭,伴随 MMP-2 下调以及 FAK、Src 和 ERK 通路失活。这些发现表明 SAA 在抑制 NPC 侵袭和转移方面具有一定的应用价值。

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