Systems pharmacology in combination with proteomics reveals underlying mechanisms of Xihuang pill against triple-negative breast cancer.
Systems pharmacology in combination with proteomics reveals underlying mechanisms of Xihuang pill against triple-negative breast cancer.
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系统药理学结合蛋白质组学研究揭示西黄丸抗三阴性乳腺癌的机制。
DOI：
10.1080/21655979.2020.1834726
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发表时间：
2020-12
期刊：
影响因子：
4.9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xu X;Zhang J;Zhang Z;Wang M;Liu Y;Li X
西黄丸（XHP）是一种传统中药配方，通过抑制癌细胞侵袭和增殖、促进癌细胞凋亡，在临床上用于治疗三阴性乳腺癌（TNBC）。但其抗TNBC生物活性成分及可能的作用机制仍不清楚。在此，通过整合系统药理学方法和体外蛋白质组学分析，系统地阐明了 XHP 抗 TNBC 的核心生物活性化合物和潜在机制。通过系统药理学分析和分子对接评估，鉴定出XHP的28种生物活性化合物和10个潜在治疗靶点。功能分析显示，针对TNBC的核心治疗靶点主要涉及表皮生长因子受体（EGFR）-磷脂酰肌醇3-激酶（PI3K）-AKT信号通路，以阻止癌细胞增殖和血管生成，以及增强癌细胞凋亡。体外蛋白质组学分析鉴定出153个差异表达蛋白（DEP），包括HASP90AA1、AKT1和EGFR，通过系统药理学分析也将其确定为TNBC的治疗靶点。蛋白功能分析表明DEPs主要参与PI3K-AKT信号通路，与系统药理学结果一致，提示系统药理学分析的可靠性。这些研究结果揭示了XHP抗TNBC的潜在机制，为中医药的合理发展提供了科学方法。
Xihuang pill (XHP), a traditional Chinese herbal formula, has been clinically used as an adjuvant therapy against triple-negative breast cancer (TNBC) via inhibiting cancer cell invasion and proliferation, as well as promoting cancer cell apoptosis. However, its anti-TNBC bio-active ingredients and possible mechanisms are still unclear. Herein, the hub bio-active compounds and underlying mechanisms of XHP against TNBC were systematically elucidated by integrating systems pharmacology approach and in vitro proteomics analysis. Using systems pharmacology analysis and molecular docking evaluation, 28 bio-active compounds and 10 potential therapeutic targets of XHP were identified. Functional analysis showed that the core therapeutic targets against TNBC were mainly involved in epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway to prevent cancer cell proliferation and angiogenesis, as well as to enhance cancer cell apoptosis. The in vitro proteomics analysis identified 153 differentially expressed proteins (DEPs), including HASP90AA1, AKT1, and EGFR, which were also identified as therapeutic targets against TNBC through systems pharmacology analysis. Protein function analysis showed that the DEPs were mainly involved in PI3K-AKT signaling pathway, which was consistent with the result of systems pharmacology, suggesting the reliability of systems pharmacology analysis. Taken together, these findings uncover the underlying mechanism of XHP against TNBC, and provide a scientific method for the rational development of traditional Chinese medicine.
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影响因子：
--
作者：
Khan MF;Nahar N;Rashid RB;Chowdhury A;Rashid MA
通讯作者：
Rashid MA
影响因子：
14.9
作者：
Kim S;Thiessen PA;Bolton EE;Chen J;Fu G;Gindulyte A;Han L;He J;He S;Shoemaker BA;Wang J;Yu B;Zhang J;Bryant SH
通讯作者：
Bryant SH
影响因子：
8
作者：
Kennedy, Sean P.;O'Neill, Michael;Hennessy, Bryan T.
通讯作者：
Hennessy, Bryan T.
DOI：
10.1186/bcr3168
发表时间：
2012-04-17
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Cheng Q;Chang JT;Geradts J;Neckers LM;Haystead T;Spector NL;Lyerly HK
通讯作者：
Lyerly HK
DOI：
10.1155/2015/854307
发表时间：
2015
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Guo Q;Lin J;Liu R;Gao Y;He S;Xu X;Hua B;Li C;Hou W;Zheng H;Bao Y
通讯作者：
Bao Y