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胡黄连碱A对人肺癌A549细胞系的体外和体内抗肿瘤活性

In vitro and in vivo antitumor activity of scutebarbatine A on human lung carcinoma A549 cell lines.

作者信息

Yang Xiao-Kun, Xu Ming-Yuan, Xu Gui-Sen, Zhang Yu-Lan, Xu Zhao-Xia

机构信息

Department of Emergency, Chengdu Military General Hospital, Chengdu 610083, China.

出版信息

Molecules. 2014 Jun 25;19(7):8740-51. doi: 10.3390/molecules19078740.

DOI:10.3390/molecules19078740
PMID:24968330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6270914/
Abstract

During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.

摘要

在我们对半枝莲抗癌活性的系统研究中，发现半枝莲中的主要生物碱之一——半枝莲碱A（SBT - A）对A549细胞具有抗肿瘤作用。因此，我们设计了本研究以详细探究SBT - A的抗肿瘤作用。通过MTT法测定SBT - A对体外培养的A549细胞的细胞毒性作用，并通过IC50值进行评估。此外，Hoechst 33258和Annexin V/PI染色分析结果表明，SBT - A通过诱导凋亡对A549细胞具有显著的抗肿瘤作用，且呈浓度依赖性。更重要的是，通过蛋白质印迹法探究其作用机制，我们的研究表明SBT - A可上调A549细胞中细胞色素c、半胱天冬酶 - 3和9的表达，并下调Bcl - 2的水平。最后，通过移植瘤裸鼠在体内评估SBT - A的抗肿瘤作用，结果证实SBT - A通过线粒体介导的凋亡对A549癌具有显著的抗肿瘤作用。总的来说，我们的结果表明，SBT - A通过上调半胱天冬酶 - 3和9的表达以及下调Bcl - 2，在体内和体外对A549细胞均显示出显著的抗肿瘤作用，其作用机制为线粒体介导的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/2320f5dfd9f9/molecules-19-08740-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/c91fc1da834a/molecules-19-08740-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/5574cd1c905b/molecules-19-08740-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/c0feea445c3f/molecules-19-08740-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/66108c7fddae/molecules-19-08740-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/36fda327e99f/molecules-19-08740-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/2320f5dfd9f9/molecules-19-08740-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/c91fc1da834a/molecules-19-08740-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/5e235f7fdaae/molecules-19-08740-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/5574cd1c905b/molecules-19-08740-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/32985cc48c10/molecules-19-08740-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/c0feea445c3f/molecules-19-08740-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/66108c7fddae/molecules-19-08740-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/36fda327e99f/molecules-19-08740-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e9f/6270914/2320f5dfd9f9/molecules-19-08740-g008.jpg

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