Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.
Network-pharmacology-based validation of TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer development and metastasis.
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基于网络药理学验证 TAMS/CXCL-1 作为消痞方预防乳腺癌发展和转移的关键介质
DOI：
10.1038/s41598-017-15030-3
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发表时间：
2017-11-06
影响因子：
4.6
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Wang N;Zheng Y;Gu J;Cai Y;Wang S;Zhang F;Chen J;Situ H;Lin Y;Wang Z
网络药理学已成为阐释中药治疗癌症作用机制的有力手段。本研究旨在验证临床方剂消癖方对乳腺癌的预防作用及其分子机制。体内乳腺癌异种移植数据显示，消癖方延缓了乳腺癌进展，有效抑制了肺转移，同时带来生存获益延长且降低了癌症干细胞亚群数量。然而，在细胞模型中未观察到类似现象。草药 - 成分 - 靶点网络分析进一步确定了81个与消癖方乳腺癌化学预防作用密切相关的基因。细胞因子芯片分析在体内外进一步验证了CXCL - 1是消癖方的关键靶点。作用机制评估表明，给予CXCL - 1可显著消除消癖方对乳腺癌迁移、侵袭、干细胞亚群、上皮 - 间充质转化（EMT）或乳腺球形成能力的转移抑制作用。总体而言，我们的研究提供了实验证据和分子机制，这可能有助于安全有效地使用草药预防乳腺癌生长或转移，并可能催生基于CXCL - 1的乳腺恶性肿瘤治疗策略。
Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer.In vivobreast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI bothin vitroandin vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities. Overall, our study provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies.
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影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
254.7
作者：
DeSantis, Carol E.;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2.1
作者：
Euhus, David M.;Diaz, Jennifer
通讯作者：
Diaz, Jennifer
影响因子：
8.1
作者：
Lin, Hongsheng;Liu, Jie;Zhang, Ying
通讯作者：
Zhang, Ying
DOI：
10.1186/s13058-017-0826-5
发表时间：
2017-03-24
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Padamsee TJ;Wills CE;Yee LD;Paskett ED
通讯作者：
Paskett ED