Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments
Background:Dendrobium nobile (D. nobile), a traditional Chinese medicine, has received attention as an anti-tumor drug, but its mechanism is still unclear. In this study, we applied network pharmacology, bioinformatics, and in vitro experiments to explore the effect and mechanism of Dendrobin A, the...
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| Format: | Article |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1079539/full |
| _version_ | 1811162600707194880 |
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| author | Xiaoqing Xu Yaping Yu Li Yang Bingshu Wang Yonghao Fan Banzhan Ruan Xiaodian Zhang Haofu Dai Wenli Mei Wei Jie Shaojiang Zheng Shaojiang Zheng |
| author_facet | Xiaoqing Xu Yaping Yu Li Yang Bingshu Wang Yonghao Fan Banzhan Ruan Xiaodian Zhang Haofu Dai Wenli Mei Wei Jie Shaojiang Zheng Shaojiang Zheng |
| author_sort | Xiaoqing Xu |
| collection | DOAJ |
| description | Background:Dendrobium nobile (D. nobile), a traditional Chinese medicine, has received attention as an anti-tumor drug, but its mechanism is still unclear. In this study, we applied network pharmacology, bioinformatics, and in vitro experiments to explore the effect and mechanism of Dendrobin A, the active ingredient of D. nobile, against pancreatic ductal adenocarcinoma (PDAC).Methods: The databases of SwissTargetPrediction and PharmMapper were used to obtain the potential targets of Dendrobin A, and the differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The protein-protein interaction (PPI) network for Dendrobin A anti-PDAC targets was constructed based on the STRING database. Molecular docking was used to assess Dendrobin A anti-PDAC targets. PLAU, one of the key targets of Dendrobin A anti-PDAC, was immunohistochemically stained in clinical tissue arrays. Finally, in vitro experiments were used to validate the effects of Dendrobin A on PLAU expression and the proliferation, apoptosis, cell cycle, migration, and invasion of PDAC cells.Results: A total of 90 genes for Dendrobin A anti-PDAC were screened, and a PPI network for Dendrobin A anti-PDAC targets was constructed. Notably, a scale-free module with 19 genes in the PPI indicated that the PPI is highly credible. Among these 19 genes, PLAU was positively correlated with the cachexia status while negatively correlated with the overall survival of PDAC patients. Through molecular docking, Dendrobin A was found to bind to PLAU, and the Dendrobin A treatment led to an attenuated PLAU expression in PDAC cells. Based on clinical tissue arrays, PLAU protein was highly expressed in PDAC cells compared to normal controls, and PLAU protein levels were associated with the differentiation and lymph node metastatic status of PDAC. In vitro experiments further showed that Dendrobin A treatment significantly inhibited the proliferation, migration, and invasion, inducing apoptosis and arresting the cell cycle of PDAC cells at the G2/M phase.Conclusion: Dendrobin A, a representative active ingredient of D. nobile, can effectively fight against PDAC by targeting PLAU. Our results provide the foundation for future PDAC treatment based on D. nobile. |
| first_indexed | 2024-04-10T06:32:04Z |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T06:32:04Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-93adacf7dc894c3f86f18d391b5624a92023-03-01T06:01:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10795391079539Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experimentsXiaoqing Xu0Yaping Yu1Li Yang2Bingshu Wang3Yonghao Fan4Banzhan Ruan5Xiaodian Zhang6Haofu Dai7Wenli Mei8Wei Jie9Shaojiang Zheng10Shaojiang Zheng11Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaKey Laboratory of Natural Products Research and Development from Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaKey Laboratory of Natural Products Research and Development from Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, ChinaKey Laboratory of Natural Products Research and Development from Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaDepartment of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, ChinaKey Laboratory of Emergency and Trauma of Ministry of Education & Key Laboratory of Tropical Cardiovascular Diseases Research of Hainan Province & Hainan Women and Children’s Medical Center, Hainan Medical University, Haikou, ChinaBackground:Dendrobium nobile (D. nobile), a traditional Chinese medicine, has received attention as an anti-tumor drug, but its mechanism is still unclear. In this study, we applied network pharmacology, bioinformatics, and in vitro experiments to explore the effect and mechanism of Dendrobin A, the active ingredient of D. nobile, against pancreatic ductal adenocarcinoma (PDAC).Methods: The databases of SwissTargetPrediction and PharmMapper were used to obtain the potential targets of Dendrobin A, and the differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues were obtained from The Cancer Genome Atlas and Genotype-Tissue Expression databases. The protein-protein interaction (PPI) network for Dendrobin A anti-PDAC targets was constructed based on the STRING database. Molecular docking was used to assess Dendrobin A anti-PDAC targets. PLAU, one of the key targets of Dendrobin A anti-PDAC, was immunohistochemically stained in clinical tissue arrays. Finally, in vitro experiments were used to validate the effects of Dendrobin A on PLAU expression and the proliferation, apoptosis, cell cycle, migration, and invasion of PDAC cells.Results: A total of 90 genes for Dendrobin A anti-PDAC were screened, and a PPI network for Dendrobin A anti-PDAC targets was constructed. Notably, a scale-free module with 19 genes in the PPI indicated that the PPI is highly credible. Among these 19 genes, PLAU was positively correlated with the cachexia status while negatively correlated with the overall survival of PDAC patients. Through molecular docking, Dendrobin A was found to bind to PLAU, and the Dendrobin A treatment led to an attenuated PLAU expression in PDAC cells. Based on clinical tissue arrays, PLAU protein was highly expressed in PDAC cells compared to normal controls, and PLAU protein levels were associated with the differentiation and lymph node metastatic status of PDAC. In vitro experiments further showed that Dendrobin A treatment significantly inhibited the proliferation, migration, and invasion, inducing apoptosis and arresting the cell cycle of PDAC cells at the G2/M phase.Conclusion: Dendrobin A, a representative active ingredient of D. nobile, can effectively fight against PDAC by targeting PLAU. Our results provide the foundation for future PDAC treatment based on D. nobile.https://www.frontiersin.org/articles/10.3389/fphar.2023.1079539/fullpancreatic ductal adenocarcinomaDendrobium nobileDendrobin Anetwork pharmacologybioinformaticsPLAU |
| spellingShingle | Xiaoqing Xu Yaping Yu Li Yang Bingshu Wang Yonghao Fan Banzhan Ruan Xiaodian Zhang Haofu Dai Wenli Mei Wei Jie Shaojiang Zheng Shaojiang Zheng Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments Frontiers in Pharmacology pancreatic ductal adenocarcinoma Dendrobium nobile Dendrobin A network pharmacology bioinformatics PLAU |
| title | Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments |
| title_full | Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments |
| title_fullStr | Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments |
| title_full_unstemmed | Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments |
| title_short | Integrated analysis of Dendrobium nobile extract Dendrobin A against pancreatic ductal adenocarcinoma based on network pharmacology, bioinformatics, and validation experiments |
| title_sort | integrated analysis of dendrobium nobile extract dendrobin a against pancreatic ductal adenocarcinoma based on network pharmacology bioinformatics and validation experiments |
| topic | pancreatic ductal adenocarcinoma Dendrobium nobile Dendrobin A network pharmacology bioinformatics PLAU |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1079539/full |
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