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樟芝通过调节人结肠癌细胞中的紧密连接蛋白-1和Wnt/β-连环蛋白信号通路来抑制转移和上皮-间质转化。

Antrodia camphorata inhibits metastasis and epithelial-to-mesenchymal transition via the modulation of claudin-1 and Wnt/β-catenin signaling pathways in human colon cancer cells.

作者信息

Hseu You-Cheng, Chao Yu-Hsien, Lin Kai-Yuan, Way Tzong-Der, Lin Hui-Yi, Thiyagarajan Varadharajan, Yang Hsin-Ling

机构信息

Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan.

Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 40402, Taiwan.

出版信息

J Ethnopharmacol. 2017 Aug 17;208:72-83. doi: 10.1016/j.jep.2017.07.001. Epub 2017 Jul 5.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Antrodia camphorata (AC) is a well known traditional Chinese medicinal mushroom in Taiwan, has been used to treat various diseases including cancer.

MATERIALS AND METHODS

In this study, we investigated the anti-metastatic and anti-EMT properties of a fermented culture broth of AC in human colon SW480 and metastatic SW620 cancer cells in vitro.

RESULTS

AC down-regulates claudin-1 and inhibits the proliferation and colony-formation abilities of both SW620 and SW480 cells. In highly metastatic SW620 cells, non-cytotoxic concentrations of AC significantly inhibited migration/invasion, accompanied by the down-regulation of MMP-2 and MMP-9 proteins. AC decreased nuclear translocation of Wnt/β-catenin through a GSK3β-dependent pathway. AC consistently inhibited EMT by up-regulating the epithelial and downregulating the mesenchymal marker proteins. In SW480 cells, AC suppressed migration/invasion potentially through the inhibition of the PI3K/AKT/NFκB signaling pathways without altering the expression levels of β-catenin and GSK3β proteins.

CONCLUSION

Altogether, this study demonstrates the anti-metastatic and anti-EMT activities of AC, which may contribute to the development of a chemopreventive agent for colon cancer.

摘要

民族药理学相关性

樟芝是台湾一种著名的传统中药蘑菇,已被用于治疗包括癌症在内的各种疾病。

材料与方法

在本研究中,我们在体外研究了樟芝发酵培养液对人结肠SW480细胞和转移性SW620癌细胞的抗转移和抗上皮-间质转化(EMT)特性。

结果

樟芝下调紧密连接蛋白-1,并抑制SW620和SW480细胞的增殖及集落形成能力。在高转移性SW620细胞中,非细胞毒性浓度的樟芝显著抑制迁移/侵袭,同时下调基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)蛋白的表达。樟芝通过糖原合成酶激酶3β(GSK3β)依赖的途径减少Wnt/β-连环蛋白的核转位。樟芝通过上调上皮标记蛋白并下调间质标记蛋白持续抑制EMT。在SW480细胞中,樟芝可能通过抑制磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/核因子κB(NFκB)信号通路来抑制迁移/侵袭,而不改变β-连环蛋白和GSK3β蛋白的表达水平。

结论

总之,本研究证明了樟芝的抗转移和抗EMT活性,这可能有助于开发一种结肠癌化学预防剂。

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