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苦玄参内酯通过调节组织蛋白酶 L 表达、MAPK 通路和上皮间质转化抑制人口腔癌细胞转移。

PlatyphyllenoneExerts Anti-Metastatic Effects on Human Oral Cancer Cells by Modulating Cathepsin L Expression, MAPK Pathway and Epithelial-Mesenchymal Transition.

机构信息

Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan.

Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua 500, Taiwan.

出版信息

Int J Mol Sci. 2021 May 9;22(9):5012. doi: 10.3390/ijms22095012.

Abstract

Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased β-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial-mesenchymal transition process.

摘要

晚期伴淋巴结转移的口腔癌预后不良,死亡率高。尽管癌症治疗的最新进展有效改善了口腔癌的预后,但大多数治疗干预措施费用高昂,并伴有严重的副作用。在本研究中,我们研究了二芳基庚烷衍生物platypyllenone 调节人口腔癌细胞转移潜能的功效。具体来说,我们用不同浓度的 platypyllenone 处理人口腔癌细胞(FaDu、Ca9-22 和 HSC3),并测量细胞增殖、迁移和侵袭。研究结果表明,platypyllenone 显著抑制人口腔癌细胞的运动性、迁移和侵袭。从机制上讲,platypyllenone 降低了 p38 磷酸化,减少了 β-catenin 和 Slug,增加了 E-cadherin 的表达,降低了组织蛋白酶 L 的表达,这共同导致癌细胞迁移和侵袭减少。综上所述,我们的研究表明,platypyllenone 通过调节组织蛋白酶 L 表达、MAPK 信号通路和上皮-间充质转化过程,对口腔癌细胞发挥显著的抗转移作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d72e/8125947/88c8b37828d1/ijms-22-05012-g001.jpg

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