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从……分离出的安妥明-H部分通过使粘着斑激酶-细胞外信号调节激酶-CCAAT/增强子结合蛋白β/c-原癌基因Fos-基质金属蛋白酶-7信号通路失活来抑制肾癌细胞侵袭。 （注：原文中“from”后面内容缺失）

Antcin-H Isolated from Inhibits Renal Cancer Cell Invasion Partly through Inactivation of FAK-ERK-C/EBP-/c-Fos-MMP-7 Pathways.

作者信息

Chiu Kun-Yuan, Chen Tzu-Hsiu, Wen Chi-Luan, Lai Jin-Mei, Cheng Chi-Chih, Liu Hsiang-Chun, Hsu Shih-Lan, Tzeng Yew-Min

机构信息

Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, Taiwan.

Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.

出版信息

Evid Based Complement Alternat Med. 2017;2017:5052870. doi: 10.1155/2017/5052870. Epub 2017 Nov 2.

DOI:10.1155/2017/5052870
PMID:29234409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5688354/
Abstract

Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC value (for 48 h) was 170 M. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 M); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression. Luciferase reporter assay showed that antcin-H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP- transactivation abilities. Moreover, antcin-H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP- and c-Fos on the upstream/enhancer region of MMP-7 promoter. Overall, this study demonstrated that the anti-invasive effect of antcin-H in human renal carcinoma 786-0 cells might be at least in part by abrogating focal adhesion complex and lamellipodium formation through inhibiting the Src/FAK-paxillin signaling pathways and decreasing MMP-7 expression through suppressing the ERK1/2-AP-1/c-Fos and C/EBP- signaling axis. Our findings provide the evidence that antcin-H may be an active component existing in with anticancer effect.

摘要

安特新-H是一种天然三萜类化合物，从台湾一种著名的抗癌药用蘑菇中提纯而来。本研究表明，安特新-H抑制人肾癌细胞786-0的生长；其IC值（48小时）为170μM。此外，在非细胞毒性浓度（<100μM）下，安特新-H抑制786-0细胞的迁移和侵袭；这些过程伴随着FAK和Src激酶活性的抑制、桩蛋白磷酸化的降低、片状伪足形成的受损以及金属蛋白酶组织抑制因子（TIMPs）的上调和基质金属蛋白酶（MMPs）的下调，尤其是MMP-7表达的下调。荧光素酶报告基因检测表明，安特新-H抑制MMP-7启动子活性，同时抑制c-Fos/AP-1和C/EBP-β的反式激活能力。此外，安特新-H抑制ERK1/2的活性，并降低C/EBP-β和c-Fos与MMP-7启动子上游/增强子区域的结合能力。总体而言，本研究表明，安特新-H对人肾癌细胞786-0的抗侵袭作用可能至少部分是通过抑制Src/FAK-桩蛋白信号通路来消除粘着斑复合体和片状伪足的形成，并通过抑制ERK1/2-AP-1/c-Fos和C/EBP-β信号轴来降低MMP-7的表达。我们的研究结果提供了证据，表明安特新-H可能是该抗癌蘑菇中具有抗癌作用的活性成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/6c1eaae6905c/ECAM2017-5052870.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/aa79ec37c40a/ECAM2017-5052870.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/b5a79178d4ba/ECAM2017-5052870.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/4db38c62504c/ECAM2017-5052870.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/eb82f9f94ad3/ECAM2017-5052870.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/64e56b4edc11/ECAM2017-5052870.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/41198cc192d0/ECAM2017-5052870.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/6c1eaae6905c/ECAM2017-5052870.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/aa79ec37c40a/ECAM2017-5052870.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/b5a79178d4ba/ECAM2017-5052870.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/4db38c62504c/ECAM2017-5052870.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/eb82f9f94ad3/ECAM2017-5052870.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/64e56b4edc11/ECAM2017-5052870.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/41198cc192d0/ECAM2017-5052870.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a8f/5688354/6c1eaae6905c/ECAM2017-5052870.007.jpg

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