The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology
Abstract Shancigu has traditionally been used for clearing heat, detoxification, resolving phlegm, and dissipating masses. However, its potential mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to explore the molecular mechanisms of Shancigu and its active compound in CRC. The...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-04795-7 |
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| author | Guiying Li Xiuqiong Zhu Ruixia Zhao Xi Zhang Cuimei Huang Miaomiao Shu Liangying Liu Jie Yuan |
| author_facet | Guiying Li Xiuqiong Zhu Ruixia Zhao Xi Zhang Cuimei Huang Miaomiao Shu Liangying Liu Jie Yuan |
| author_sort | Guiying Li |
| collection | DOAJ |
| description | Abstract Shancigu has traditionally been used for clearing heat, detoxification, resolving phlegm, and dissipating masses. However, its potential mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to explore the molecular mechanisms of Shancigu and its active compound in CRC. The active ingredients of Shancigu and their predicted targets were identified, and differentially expressed genes (DEGs) associated with CRC metastasis and invasion were screened. Intersection genes were obtained and used to construct a protein–protein interaction (PPI) network. Core genes were identified, and their prognostic significance was analyzed. Molecular docking was performed between key survival-related genes and Shancigu compounds. Further in vitro, organoid, and in vivo experiments were conducted to investigate the regulatory effects of Stigmasterol, a major active component. A total of 18 active ingredients and 366 potential targets of Shancigu were identified. From 19,331 DEGs, 365 intersection genes and 18 core genes were screened. Among them, AKT1, AR, FN1, HRAS, ITGB1, and JUN showed significant prognostic relevance in CRC. Molecular docking revealed that Stigmasterol strongly binds to ITGB1 and JUN. In cellular experiments, Stigmasterol inhibited viability, proliferation, migration, and invasion, induced apoptosis, and downregulated JUN and ITGB1 expressions in HCT116 and Caco-2 cells. In CRC organoids, Stigmasterol reduced organoid viability and ATP activity. Animal studies demonstrated that both Shancigu and Stigmasterol reduced tumor weight and volume and inhibited Ki67, ITGB1, and JUN expression. Stigmasterol may suppress CRC proliferation and invasion by targeting the key genes JUN and ITGB1, providing insights into the potential therapeutic mechanisms of Shancigu against CRC. |
| format | Article |
| id | doaj-art-ab6c00f0d7fb4eb8945d62b2f7bd9c8d |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ab6c00f0d7fb4eb8945d62b2f7bd9c8d2025-08-20T03:45:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-04795-7The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacologyGuiying Li0Xiuqiong Zhu1Ruixia Zhao2Xi Zhang3Cuimei Huang4Miaomiao Shu5Liangying Liu6Jie Yuan7Foshan Clinical Medical School, Guangzhou University of Chinese MedicineDepartment of Pediatric Surgery, Foshan Fosun Chancheng HospitalDepartment of General Surgery, Foshan Fosun Chancheng HospitalDepartment of Surgery, Foshan Fosun Chancheng HospitalDepartment of Surgery, Foshan Fosun Chancheng HospitalDepartment of General Surgery, Foshan Fosun Chancheng HospitalDepartment of General Surgery, Foshan Fosun Chancheng HospitalFoshan Clinical Medical School, Guangzhou University of Chinese MedicineAbstract Shancigu has traditionally been used for clearing heat, detoxification, resolving phlegm, and dissipating masses. However, its potential mechanisms in colorectal cancer (CRC) remain unclear. This study aimed to explore the molecular mechanisms of Shancigu and its active compound in CRC. The active ingredients of Shancigu and their predicted targets were identified, and differentially expressed genes (DEGs) associated with CRC metastasis and invasion were screened. Intersection genes were obtained and used to construct a protein–protein interaction (PPI) network. Core genes were identified, and their prognostic significance was analyzed. Molecular docking was performed between key survival-related genes and Shancigu compounds. Further in vitro, organoid, and in vivo experiments were conducted to investigate the regulatory effects of Stigmasterol, a major active component. A total of 18 active ingredients and 366 potential targets of Shancigu were identified. From 19,331 DEGs, 365 intersection genes and 18 core genes were screened. Among them, AKT1, AR, FN1, HRAS, ITGB1, and JUN showed significant prognostic relevance in CRC. Molecular docking revealed that Stigmasterol strongly binds to ITGB1 and JUN. In cellular experiments, Stigmasterol inhibited viability, proliferation, migration, and invasion, induced apoptosis, and downregulated JUN and ITGB1 expressions in HCT116 and Caco-2 cells. In CRC organoids, Stigmasterol reduced organoid viability and ATP activity. Animal studies demonstrated that both Shancigu and Stigmasterol reduced tumor weight and volume and inhibited Ki67, ITGB1, and JUN expression. Stigmasterol may suppress CRC proliferation and invasion by targeting the key genes JUN and ITGB1, providing insights into the potential therapeutic mechanisms of Shancigu against CRC.https://doi.org/10.1038/s41598-025-04795-7Network pharmacologyShanciguStigmasterolITGB1JUNColorectal cancer |
| spellingShingle | Guiying Li Xiuqiong Zhu Ruixia Zhao Xi Zhang Cuimei Huang Miaomiao Shu Liangying Liu Jie Yuan The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology Scientific Reports Network pharmacology Shancigu Stigmasterol ITGB1 JUN Colorectal cancer |
| title | The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| title_full | The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| title_fullStr | The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| title_full_unstemmed | The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| title_short | The mechanism of Shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| title_sort | mechanism of shancigu and its monomer in the development of colorectal cancer based on network pharmacology |
| topic | Network pharmacology Shancigu Stigmasterol ITGB1 JUN Colorectal cancer |
| url | https://doi.org/10.1038/s41598-025-04795-7 |
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