Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway
Abstract Objective Colorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adver...
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| Format: | Article |
| Language: | English |
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BMC
2025-04-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00412-9 |
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| author | Peng Shen Shunli Wu Yi Chen Guangjing Feng Xue Guo Yingguo Chen Zhigang Wang Youfeng Shen Hongbo Wang Ke Li |
| author_facet | Peng Shen Shunli Wu Yi Chen Guangjing Feng Xue Guo Yingguo Chen Zhigang Wang Youfeng Shen Hongbo Wang Ke Li |
| author_sort | Peng Shen |
| collection | DOAJ |
| description | Abstract Objective Colorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adverse reactions of CRC, its core active components and mechanism of action remain unclear. Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells. Methods The The Cancer Genome Atlas (TCGA) database was integrated with network pharmacology analysis to screen for the key target of CRC, Gomisin B, and its associated TLR4/NF-κB pathway. Through in vitro CRC stem cell models and mouse xenograft tumor models, techniques such as CCK-8, Transwell, flow cytometry, qPCR/WB were used to evaluate the effects of YGS and Gomisin B on proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT), and to detect the expression of TLR4 and downstream inflammatory factors. Results Both YGS and Gomisin B inhibited the proliferation, migration and invasion of CRC stem cells and tumor tissues. Meanwhile, they promoted apoptosis but reduced the expression of the inflammatory factor TLR4 and proteins associated with the NF-κB pathway, thereby exerting suppressive effects on tumorigenesis and disease progression. YGS might also impede EMT progression through modulation of the NF-κB pathway. Conclusion This study for the first time elucidated the dual anti-tumor mechanisms of YGS, which sensitized CRC stem cells and inhibited immune escape by targeting the TLR4/NF-κB pathway through Gomisin B. It provides a pharmacological basis for the modern research of traditional Chinese medicine compound against CRC. Clinical trial number Not applicable. |
| format | Article |
| id | doaj-art-b0f429e1d4f44cb68381aad3f172d354 |
| institution | OA Journals |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-b0f429e1d4f44cb68381aad3f172d3542025-08-20T02:17:50ZengBMCHereditas1601-52232025-04-01162112010.1186/s41065-025-00412-9Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathwayPeng Shen0Shunli Wu1Yi Chen2Guangjing Feng3Xue Guo4Yingguo Chen5Zhigang Wang6Youfeng Shen7Hongbo Wang8Ke Li9Department of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalInfection Control Department, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of Laboratory Medicine, Chongqing Precision Medical Industry Technology Research InstituteDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalDepartment of General Surgery, Chongqing Traditional Chinese Medicine HospitalAbstract Objective Colorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adverse reactions of CRC, its core active components and mechanism of action remain unclear. Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells. Methods The The Cancer Genome Atlas (TCGA) database was integrated with network pharmacology analysis to screen for the key target of CRC, Gomisin B, and its associated TLR4/NF-κB pathway. Through in vitro CRC stem cell models and mouse xenograft tumor models, techniques such as CCK-8, Transwell, flow cytometry, qPCR/WB were used to evaluate the effects of YGS and Gomisin B on proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT), and to detect the expression of TLR4 and downstream inflammatory factors. Results Both YGS and Gomisin B inhibited the proliferation, migration and invasion of CRC stem cells and tumor tissues. Meanwhile, they promoted apoptosis but reduced the expression of the inflammatory factor TLR4 and proteins associated with the NF-κB pathway, thereby exerting suppressive effects on tumorigenesis and disease progression. YGS might also impede EMT progression through modulation of the NF-κB pathway. Conclusion This study for the first time elucidated the dual anti-tumor mechanisms of YGS, which sensitized CRC stem cells and inhibited immune escape by targeting the TLR4/NF-κB pathway through Gomisin B. It provides a pharmacological basis for the modern research of traditional Chinese medicine compound against CRC. Clinical trial number Not applicable.https://doi.org/10.1186/s41065-025-00412-9Gomisin BTLR4Inflammatory factorNetwork pharmacology |
| spellingShingle | Peng Shen Shunli Wu Yi Chen Guangjing Feng Xue Guo Yingguo Chen Zhigang Wang Youfeng Shen Hongbo Wang Ke Li Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway Hereditas Gomisin B TLR4 Inflammatory factor Network pharmacology |
| title | Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway |
| title_full | Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway |
| title_fullStr | Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway |
| title_full_unstemmed | Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway |
| title_short | Yi Gong San inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the NF-κB pathway |
| title_sort | yi gong san inhibits tumor immune escape by sensitizing colorectal cancer stem cells via the nf κb pathway |
| topic | Gomisin B TLR4 Inflammatory factor Network pharmacology |
| url | https://doi.org/10.1186/s41065-025-00412-9 |
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