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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Research Network of Computational and Structural Biotechnology
2020
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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. |
format | Online Article Text |
id | pubmed-7260686 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Research Network of Computational and Structural Biotechnology |
record_format | MEDLINE/PubMed |
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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