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藤梨根提取物通过下调 MEK/ERK 通路抑制基质金属蛋白酶-2 的活性来减弱口腔癌细胞的转移潜能。

Duchesnea indica extract attenuates oral cancer cells metastatic potential through the inhibition of the matrix metalloproteinase-2 activity by down-regulating the MEK/ERK pathway.

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.

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

出版信息

Phytomedicine. 2019 Oct;63:152960. doi: 10.1016/j.phymed.2019.152960. Epub 2019 May 16.

DOI:10.1016/j.phymed.2019.152960
PMID:31280137
Abstract

BACKGROUND

Duchesnea indica (Andr.) Focke, an herb in folk medicine used extensively in traditional Chinese medicine, has cytostatic properties as well as antioxidant and antimetastasis activities in various cancer cells. However, the effects and underlying mechanisms of Duchesnea indica extracts (DIEs) on human oral squamous cell carcinoma (OSCC) metastases remain unclear.

PURPOSE

In this study, we posit the hypothesis that DIE possesses antimetastatic effects on human OSCC cells.

METHODS

The effects of DIE on cell viability, motility, migration, and invasion were investigated. Gelatin zymography, Western blotting, migration and invasion assays were used to further study the underlying mechanisms involved in the antimetastatic effects of DIE in OSCC cells.

RESULTS

The results from MTT assay revealed that DIE did not affect the cell viability of OSCC cells. Moreover, DIE significantly attenuated OSCC cells' motility, migration, and invasion by reducing the MMP-2 protein expression and MMP-2 activity in a dose-dependent manner. In addition, DIE reduced the phosphorylation of both ERK1/2 and its upstream kinase but had no effect on the phosphorylation of p38 and JNK.

CONCLUSION

DIE triggers the antimetastatic activity in OSCC cells by suppressing the MMP-2 activity via the MEK/ERK signaling pathways. Therefore, these findings are promising for the use of DIE antimetastatic activity in oral cancer metastasis treatment.

摘要

背景

藤梨根(Duchesnea indica (Andr.) Focke)是民间药物中的一种草药,在传统中药中被广泛使用,具有细胞抑制特性以及在各种癌细胞中具有抗氧化和抗转移活性。然而,藤梨根提取物(DIEs)对人口腔鳞状细胞癌(OSCC)转移的影响及其潜在机制尚不清楚。

目的

本研究假设 DIE 对人 OSCC 细胞具有抗转移作用。

方法

研究了 DIE 对细胞活力、运动性、迁移和侵袭的影响。明胶酶谱法、Western blot 分析、迁移和侵袭试验用于进一步研究 DIE 在 OSCC 细胞中抗转移作用的潜在机制。

结果

MTT 检测结果表明,DIE 不影响 OSCC 细胞的细胞活力。此外,DIE 通过以剂量依赖的方式降低 MMP-2 蛋白表达和 MMP-2 活性,显著减弱 OSCC 细胞的运动性、迁移和侵袭能力。此外,DIE 减少了 ERK1/2 及其上游激酶的磷酸化,但对 p38 和 JNK 的磷酸化没有影响。

结论

DIE 通过 MEK/ERK 信号通路抑制 MMP-2 活性,引发 OSCC 细胞的抗转移活性。因此,这些发现有望将 DIE 的抗转移活性用于口腔癌转移的治疗。

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