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A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation

BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overco...

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Autores principales: Wu, Chao, Huang, Zhi-Hong, Meng, Zi-Qi, Fan, Xiao-Tian, Lu, Shan, Tan, Ying-Ying, You, Lei-Ming, Huang, Jia-Qi, Stalin, Antony, Ye, Pei-Zhi, Wu, Zhi-Shan, Zhang, Jing-Yuan, Liu, Xin-Kui, Zhou, Wei, Zhang, Xiao-Meng, Wu, Jia-Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607619/
https://www.ncbi.nlm.nih.gov/pubmed/34809653
http://dx.doi.org/10.1186/s13020-021-00534-y
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author Wu, Chao
Huang, Zhi-Hong
Meng, Zi-Qi
Fan, Xiao-Tian
Lu, Shan
Tan, Ying-Ying
You, Lei-Ming
Huang, Jia-Qi
Stalin, Antony
Ye, Pei-Zhi
Wu, Zhi-Shan
Zhang, Jing-Yuan
Liu, Xin-Kui
Zhou, Wei
Zhang, Xiao-Meng
Wu, Jia-Rui
author_facet Wu, Chao
Huang, Zhi-Hong
Meng, Zi-Qi
Fan, Xiao-Tian
Lu, Shan
Tan, Ying-Ying
You, Lei-Ming
Huang, Jia-Qi
Stalin, Antony
Ye, Pei-Zhi
Wu, Zhi-Shan
Zhang, Jing-Yuan
Liu, Xin-Kui
Zhou, Wei
Zhang, Xiao-Meng
Wu, Jia-Rui
author_sort Wu, Chao
collection PubMed
description BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-021-00534-y.
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spelling pubmed-86076192021-11-22 A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation Wu, Chao Huang, Zhi-Hong Meng, Zi-Qi Fan, Xiao-Tian Lu, Shan Tan, Ying-Ying You, Lei-Ming Huang, Jia-Qi Stalin, Antony Ye, Pei-Zhi Wu, Zhi-Shan Zhang, Jing-Yuan Liu, Xin-Kui Zhou, Wei Zhang, Xiao-Meng Wu, Jia-Rui Chin Med Research BACKGROUND: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated. METHODS: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis. RESULTS: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis. CONCLUSIONS: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13020-021-00534-y. BioMed Central 2021-11-22 /pmc/articles/PMC8607619/ /pubmed/34809653 http://dx.doi.org/10.1186/s13020-021-00534-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wu, Chao
Huang, Zhi-Hong
Meng, Zi-Qi
Fan, Xiao-Tian
Lu, Shan
Tan, Ying-Ying
You, Lei-Ming
Huang, Jia-Qi
Stalin, Antony
Ye, Pei-Zhi
Wu, Zhi-Shan
Zhang, Jing-Yuan
Liu, Xin-Kui
Zhou, Wei
Zhang, Xiao-Meng
Wu, Jia-Rui
A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title_full A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title_fullStr A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title_full_unstemmed A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title_short A network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on WGCNA and in vitro experiment validation
title_sort network pharmacology approach to reveal the pharmacological targets and biological mechanism of compound kushen injection for treating pancreatic cancer based on wgcna and in vitro experiment validation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607619/
https://www.ncbi.nlm.nih.gov/pubmed/34809653
http://dx.doi.org/10.1186/s13020-021-00534-y
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