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

Abstract 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...

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Autores principales:	Chao Wu, Zhi-Hong Huang, Zi-Qi Meng, Xiao-Tian Fan, Shan Lu, Ying-Ying Tan, Lei-Ming You, Jia-Qi Huang, Antony Stalin, Pei-Zhi Ye, Zhi-Shan Wu, Jing-Yuan Zhang, Xin-Kui Liu, Wei Zhou, Xiao-Meng Zhang, Jia-Rui Wu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Compound kushen injection Pancreatic cancer WGCNA Network pharmacology Other systems of medicine RZ201-999
Acceso en línea:	https://doaj.org/article/c79b92292800401c87710b1a1ba61dfa
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spelling	oai:doaj.org-article:c79b92292800401c87710b1a1ba61dfa2021-11-28T12:08:16ZA 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 validation10.1186/s13020-021-00534-y1749-8546https://doaj.org/article/c79b92292800401c87710b1a1ba61dfa2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13020-021-00534-yhttps://doaj.org/toc/1749-8546Abstract 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.Chao WuZhi-Hong HuangZi-Qi MengXiao-Tian FanShan LuYing-Ying TanLei-Ming YouJia-Qi HuangAntony StalinPei-Zhi YeZhi-Shan WuJing-Yuan ZhangXin-Kui LiuWei ZhouXiao-Meng ZhangJia-Rui WuBMCarticleCompound kushen injectionPancreatic cancerWGCNANetwork pharmacologyOther systems of medicineRZ201-999ENChinese Medicine, Vol 16, Iss 1, Pp 1-27 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Compound kushen injection Pancreatic cancer WGCNA Network pharmacology Other systems of medicine RZ201-999
spellingShingle	Compound kushen injection Pancreatic cancer WGCNA Network pharmacology Other systems of medicine RZ201-999 Chao Wu Zhi-Hong Huang Zi-Qi Meng Xiao-Tian Fan Shan Lu Ying-Ying Tan Lei-Ming You Jia-Qi Huang Antony Stalin Pei-Zhi Ye Zhi-Shan Wu Jing-Yuan Zhang Xin-Kui Liu Wei Zhou Xiao-Meng Zhang Jia-Rui Wu 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
description	Abstract 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.
format	article
author	Chao Wu Zhi-Hong Huang Zi-Qi Meng Xiao-Tian Fan Shan Lu Ying-Ying Tan Lei-Ming You Jia-Qi Huang Antony Stalin Pei-Zhi Ye Zhi-Shan Wu Jing-Yuan Zhang Xin-Kui Liu Wei Zhou Xiao-Meng Zhang Jia-Rui Wu
author_facet	Chao Wu Zhi-Hong Huang Zi-Qi Meng Xiao-Tian Fan Shan Lu Ying-Ying Tan Lei-Ming You Jia-Qi Huang Antony Stalin Pei-Zhi Ye Zhi-Shan Wu Jing-Yuan Zhang Xin-Kui Liu Wei Zhou Xiao-Meng Zhang Jia-Rui Wu
author_sort	Chao Wu
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_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_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_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
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c79b92292800401c87710b1a1ba61dfa
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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

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