Uncovering the anticancer mechanism of Compound Kushen Injection against HCC by integrating quantitative analysis, network analysis and experimental validation

被引:92
|
作者
Gao, Li [1 ]
Wang, Ke-xin [1 ,2 ]
Zhou, Yu-zhi [1 ]
Fang, Jian-song [3 ]
Qin, Xue-mei [1 ]
Du, Guan-hua [1 ,4 ,5 ]
机构
[1] Shanxi Univ, Modern Res Ctr Tradit Chinese Med, Taiyuan 030006, Shanxi, Peoples R China
[2] Shanxi Univ, Coll Chem & Chem Engn, Taiyuan 030006, Shanxi, Peoples R China
[3] Guangzhou Univ Chinese Med, Inst Clin Pharmacol, Guangzhou 510405, Guangdong, Peoples R China
[4] Chinese Acad Med Sci, Inst Mat Med, Beijing 100050, Peoples R China
[5] Peking Union Med Coll, Beijing 100050, Peoples R China
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
关键词
HEPATOCELLULAR-CARCINOMA; PHARMACOLOGY; METABOLISM; METABOLOMICS; ASSOCIATION; EXPRESSION; EFFICACY; DATABASE; WEB;
D O I
10.1038/s41598-017-18325-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI. Our results showed that CKI significantly suppressed the proliferation and migration of SMMC-7721 cells. Four main active compounds of CKI (matrine, oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell proliferation assays. The potential targets and pathways involved in the anti-HCC effects of CKI were predicted by a network pharmacology approach, and some of the crucial proteins and pathways were further validated by western blotting and metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of glycometabolism and amino acid metabolism. These results provide insights into the mechanism of CKI by combining quantitative analysis of components, network pharmacology and experimental validation.
引用
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页数:15
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