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Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology

As one of the classical traditional Chinese medicine (TCM) prescriptions in treating gynecological tumors, Guizhi Fuling Decoction (GFD) has been used to treat breast cancer (BRCA). Nonetheless, the potential molecular mechanism remains unclear so far. Therefore, systems pharmacology was used in com...

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Autores principales: Dai, Yifei, Qiang, Weijie, Yu, Xiankuo, Cai, Siwei, Lin, Kequan, Xie, Lan, Lan, Xun, Wang, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Research Network of Computational and Structural Biotechnology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260686/
https://www.ncbi.nlm.nih.gov/pubmed/32489526
http://dx.doi.org/10.1016/j.csbj.2020.05.004
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author Dai, Yifei
Qiang, Weijie
Yu, Xiankuo
Cai, Siwei
Lin, Kequan
Xie, Lan
Lan, Xun
Wang, Dong
author_facet Dai, Yifei
Qiang, Weijie
Yu, Xiankuo
Cai, Siwei
Lin, Kequan
Xie, Lan
Lan, Xun
Wang, Dong
author_sort Dai, Yifei
collection PubMed
description As one of the classical traditional Chinese medicine (TCM) prescriptions in treating gynecological tumors, Guizhi Fuling Decoction (GFD) has been used to treat breast cancer (BRCA). Nonetheless, the potential molecular mechanism remains unclear so far. Therefore, systems pharmacology was used in combination with high throughput sequencing-based high throughput screening (HTS(2)) assay and bioinformatic technologies in this study to investigate the molecular mechanisms of GFD in treating BRCA. By computationally analyzing 76 active ingredients in GFD, 38 potential therapeutic targets were predicted and significantly enriched in the “pathways in cancer”. Meanwhile, experimental analysis was carried out to examine changes in the expression levels of 308 genes involved in the “pathways in cancer” in BRCA cells treated by five herbs of GFD utilizing HTS(2) platform, and 5 key therapeutic targets, including HRAS, EGFR, PTK2, SOS1, and ITGB1, were identified. The binding mode of active compounds to these five targets was analyzed by molecular docking and molecular dynamics simulation. It was found after integrating the computational and experimental data that, GFD possessed the anti-proliferation, pro-apoptosis, and anti-angiogenesis activities mainly through regulating the PI3K and the MAPK signaling pathways to inhibit BRCA. Besides, consistent with the TCM theory about the synergy of Cinnamomi Ramulus (Guizhi) by Cortex Moutan (Mudanpi) in GFD, both of these two herbs acted on the same targets and pathways. Taken together, the combined application of computational systems pharmacology techniques and experimental HTS(2) platform provides a practical research strategy to investigate the functional and biological mechanisms of the complicated TCM prescriptions.
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spelling pubmed-72606862020-06-01 Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology Dai, Yifei Qiang, Weijie Yu, Xiankuo Cai, Siwei Lin, Kequan Xie, Lan Lan, Xun Wang, Dong Comput Struct Biotechnol J Research Article As one of the classical traditional Chinese medicine (TCM) prescriptions in treating gynecological tumors, Guizhi Fuling Decoction (GFD) has been used to treat breast cancer (BRCA). Nonetheless, the potential molecular mechanism remains unclear so far. Therefore, systems pharmacology was used in combination with high throughput sequencing-based high throughput screening (HTS(2)) assay and bioinformatic technologies in this study to investigate the molecular mechanisms of GFD in treating BRCA. By computationally analyzing 76 active ingredients in GFD, 38 potential therapeutic targets were predicted and significantly enriched in the “pathways in cancer”. Meanwhile, experimental analysis was carried out to examine changes in the expression levels of 308 genes involved in the “pathways in cancer” in BRCA cells treated by five herbs of GFD utilizing HTS(2) platform, and 5 key therapeutic targets, including HRAS, EGFR, PTK2, SOS1, and ITGB1, were identified. The binding mode of active compounds to these five targets was analyzed by molecular docking and molecular dynamics simulation. It was found after integrating the computational and experimental data that, GFD possessed the anti-proliferation, pro-apoptosis, and anti-angiogenesis activities mainly through regulating the PI3K and the MAPK signaling pathways to inhibit BRCA. Besides, consistent with the TCM theory about the synergy of Cinnamomi Ramulus (Guizhi) by Cortex Moutan (Mudanpi) in GFD, both of these two herbs acted on the same targets and pathways. Taken together, the combined application of computational systems pharmacology techniques and experimental HTS(2) platform provides a practical research strategy to investigate the functional and biological mechanisms of the complicated TCM prescriptions. Research Network of Computational and Structural Biotechnology 2020-05-18 /pmc/articles/PMC7260686/ /pubmed/32489526 http://dx.doi.org/10.1016/j.csbj.2020.05.004 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Dai, Yifei
Qiang, Weijie
Yu, Xiankuo
Cai, Siwei
Lin, Kequan
Xie, Lan
Lan, Xun
Wang, Dong
Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title_full Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title_fullStr Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title_full_unstemmed Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title_short Guizhi Fuling Decoction inhibiting the PI3K and MAPK pathways in breast cancer cells revealed by HTS(2) technology and systems pharmacology
title_sort guizhi fuling decoction inhibiting the pi3k and mapk pathways in breast cancer cells revealed by hts(2) technology and systems pharmacology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260686/
https://www.ncbi.nlm.nih.gov/pubmed/32489526
http://dx.doi.org/10.1016/j.csbj.2020.05.004
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