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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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-021-00534-y |
| _version_ | 1818434254209548288 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:34:04Z |
| format | Article |
| id | doaj.art-c79b92292800401c87710b1a1ba61dfa |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-12-14T16:34:04Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-c79b92292800401c87710b1a1ba61dfa2022-12-21T22:54:31ZengBMCChinese Medicine1749-85462021-11-0116112710.1186/s13020-021-00534-yA 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 validationChao Wu0Zhi-Hong Huang1Zi-Qi Meng2Xiao-Tian Fan3Shan Lu4Ying-Ying Tan5Lei-Ming You6Jia-Qi Huang7Antony Stalin8Pei-Zhi Ye9Zhi-Shan Wu10Jing-Yuan Zhang11Xin-Kui Liu12Wei Zhou13Xiao-Meng Zhang14Jia-Rui Wu15School of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Life Science, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineState Key Laboratory of Subtropical Silviculture, Department of Traditional Chinese Medicine, Zhejiang A&F UniversityNational Cancer Center/National Clinical Research Center for Cancer/Chinese Medicine Department of the Caner Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineAbstract 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.https://doi.org/10.1186/s13020-021-00534-yCompound kushen injectionPancreatic cancerWGCNANetwork pharmacology |
| spellingShingle | 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 Chinese Medicine Compound kushen injection Pancreatic cancer WGCNA Network pharmacology |
| 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 | Compound kushen injection Pancreatic cancer WGCNA Network pharmacology |
| url | https://doi.org/10.1186/s13020-021-00534-y |
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