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诃子叶提取物通过抑制基质金属蛋白酶-9 和 MAPK 通路对宫颈癌的抗肿瘤转移作用。

Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein-9 and MAPK pathway.

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

出版信息

Environ Toxicol. 2019 Jan;34(1):60-66. doi: 10.1002/tox.22657. Epub 2018 Sep 26.

DOI:10.1002/tox.22657
PMID:30259628
Abstract

The effects of Terminalia catappa leaf extracts (TCE) have been widely investigated, including its antioxidative, anti-inflammatory, and antidiabetic activity, as well as its antimetastatic effects on several types of human cancer. However, no study has examined the antimetastatic potential of TCE in cervical cancer cells. This study aimed to elucidate the potential antimetastatic properties of ethanol extracts of Terminalia catappa in 12-O-tetradecanoylphorbol-13-acetate treated human cervical cancer cells and investigate the signaling pathway of this process. We demonstrated that TCE elicited very low cytotoxicity and significantly inhibited cellular migration and invasion in human HeLa and SiHa cervical cancer cells. Moreover, the gelatin zymography, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR analysis revealed that the activity and mRNA level of matrix metalloproteinase-9 (MMP-9) were inhibited by TCE in a concentration-dependent manner. The Western blot results demonstrated that the highest concentration of TCE (100 μg/ml) reduced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) by 46% in the HeLa cell lines. In conclusion, it was revealed that TCE exerted antimetastatic effects on cervical cancer cells by inhibiting the expression of MMP-9 through the ERK1/2 pathway.

摘要

诃子叶提取物 (TCE) 的作用已得到广泛研究,包括其抗氧化、抗炎和抗糖尿病活性,以及对几种人类癌症的抗转移作用。然而,尚无研究探讨 TCE 在宫颈癌细胞中的抗转移潜力。本研究旨在阐明乙醇提取物 TCE 在十四烷酰佛波醇-13-乙酸酯处理的人宫颈癌细胞中的潜在抗转移特性,并研究该过程的信号通路。我们证明 TCE 表现出很低的细胞毒性,并显著抑制人宫颈癌细胞 HeLa 和 SiHa 的细胞迁移和侵袭。此外,明胶酶谱分析、逆转录-聚合酶链反应 (RT-PCR) 和实时 PCR 分析表明,TCE 以浓度依赖性方式抑制基质金属蛋白酶-9 (MMP-9) 的活性和 mRNA 水平。Western blot 结果表明,TCE 的最高浓度 (100μg/ml) 使 HeLa 细胞系中细胞外信号调节激酶 1/2 (ERK1/2) 的磷酸化减少了 46%。总之,研究结果表明,TCE 通过 ERK1/2 通路抑制 MMP-9 的表达对宫颈癌细胞发挥抗转移作用。

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