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佛手柑素通过阻断多种致癌信号级联和上皮-间充质转化抑制肺癌细胞转移。

Bergamottin Suppresses Metastasis of Lung Cancer Cells through Abrogation of Diverse Oncogenic Signaling Cascades and Epithelial-to-Mesenchymal Transition.

机构信息

Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Korea.

出版信息

Molecules. 2018 Jul 2;23(7):1601. doi: 10.3390/molecules23071601.

DOI:10.3390/molecules23071601
PMID:30004418
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6100248/
Abstract

Bergamottin (BGM) is a naturally occurring furanocoumarin and is known to inhibit the growth of tumor cells. However, there is no available evidence that BGM has an inhibitory effect on cancer metastasis, specifically on the epithelial-to-mesenchymal transition (EMT) process in the malignant cells. Here we aimed to evaluate the antimetastatic potential of BGM in human lung adenocarcinoma cells. Our results demonstrate that BGM can block EMT, and observed inhibition was accompanied by downregulation of fibronectin, vimentin, N-cadherin, twist and snail expression, and upregulation of occludin and E-cadherin. Interestingly, transforming growth factor-β (TGF-β)-induced upregulation of fibronectin, vimentin, N-cadherin, twist and snail, and downregulation of occludin and E-cadherin, were abrogated by BGM treatment. Moreover, the treatment of BGM repressed TGF-β-induced cell invasive potential. BGM treatment also inhibited multiple oncogenic cascades such as PI3K/Akt/mTOR. Overall, the results demonstrate the potential antimetastatic activity of BGM against lung cancer cells.

摘要

佛手柑内酯(BGM)是一种天然呋喃香豆素,已知能抑制肿瘤细胞的生长。然而,没有证据表明 BGM 对癌症转移有抑制作用,特别是对恶性细胞中的上皮-间充质转化(EMT)过程。在这里,我们旨在评估 BGM 在人肺腺癌细胞中的抗转移潜力。我们的结果表明,BGM 可以阻断 EMT,观察到的抑制伴随着纤连蛋白、波形蛋白、N-钙粘蛋白、twist 和 snail 表达的下调,以及 occludin 和 E-钙粘蛋白的上调。有趣的是,BGM 处理可阻断 TGF-β诱导的纤连蛋白、波形蛋白、N-钙粘蛋白、twist 和 snail 的上调,以及 occludin 和 E-钙粘蛋白的下调。此外,BGM 处理抑制了 TGF-β诱导的细胞侵袭潜力。BGM 处理还抑制了多个致癌级联,如 PI3K/Akt/mTOR。总的来说,这些结果表明 BGM 对肺癌细胞具有潜在的抗转移活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/79128cbc57e8/molecules-23-01601-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/1887c125278d/molecules-23-01601-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/2f587eb5e086/molecules-23-01601-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/a85aaf9e83d3/molecules-23-01601-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/79128cbc57e8/molecules-23-01601-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/1887c125278d/molecules-23-01601-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/2f587eb5e086/molecules-23-01601-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/a85aaf9e83d3/molecules-23-01601-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b4a/6100248/79128cbc57e8/molecules-23-01601-g004.jpg

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