A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer
Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.592903/full |
| _version_ | 1818866091999363072 |
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| author | Boyu Pan Yun Wang Chunnuan Wu Junrong Jia Chen Huang Senbiao Fang Liren Liu |
| author_facet | Boyu Pan Yun Wang Chunnuan Wu Junrong Jia Chen Huang Senbiao Fang Liren Liu |
| author_sort | Boyu Pan |
| collection | DOAJ |
| description | Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the assistance of network pharmacology and bioinformatic analysis tools, and found a potential therapeutic effect of DSD on cancer. Indeed, our in vivo experiment demonstrated that oral administration of DSD could significantly inhibit the growth of xenografted gastric cancer (GC) on mice. The subsequent enrichment analyses for 123 candidate core targets evacuated from the drug/disease-target protein-protein interaction network showed that DSD could affect the key biological processes involving the survival and growth of GC cells, such as apoptosis and cell cycle, and the disturbance of these biological processes is likely attributed to the simultaneous inhibition of multiple signaling pathways, including PI3K/Akt, MAPK, and p53 pathways. Notably, these in silico results were further validated by a series of cellular functional and molecular biological assays in vitro. Moreover, molecular docking analysis suggested an important role of MCM2 in delivering the pharmacological activity of DSD against GC. Together, these results indicate that our network pharmacology and bioinformatics-guided approach is feasible and useful in exploring not only the mechanism of action, but also the “new use” of the old CHM formula. |
| first_indexed | 2024-12-19T10:57:56Z |
| format | Article |
| id | doaj.art-5e2ea8a745394127848dde4b553d022c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T10:57:56Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-5e2ea8a745394127848dde4b553d022c2022-12-21T20:24:44ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.592903592903A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric CancerBoyu Pan0Yun Wang1Chunnuan Wu2Junrong Jia3Chen Huang4Senbiao Fang5Liren Liu6Department of Gastrointestinal Cancer Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Integrated Traditional and Western Medicine, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Pharmacy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaPublic Laboratory, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Gastrointestinal Cancer Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaSchool of Information Science and Engineering, Central South University, Changsha, ChinaDepartment of Gastrointestinal Cancer Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDanggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the assistance of network pharmacology and bioinformatic analysis tools, and found a potential therapeutic effect of DSD on cancer. Indeed, our in vivo experiment demonstrated that oral administration of DSD could significantly inhibit the growth of xenografted gastric cancer (GC) on mice. The subsequent enrichment analyses for 123 candidate core targets evacuated from the drug/disease-target protein-protein interaction network showed that DSD could affect the key biological processes involving the survival and growth of GC cells, such as apoptosis and cell cycle, and the disturbance of these biological processes is likely attributed to the simultaneous inhibition of multiple signaling pathways, including PI3K/Akt, MAPK, and p53 pathways. Notably, these in silico results were further validated by a series of cellular functional and molecular biological assays in vitro. Moreover, molecular docking analysis suggested an important role of MCM2 in delivering the pharmacological activity of DSD against GC. Together, these results indicate that our network pharmacology and bioinformatics-guided approach is feasible and useful in exploring not only the mechanism of action, but also the “new use” of the old CHM formula.https://www.frontiersin.org/articles/10.3389/fphar.2020.592903/fullDanggui Sini DecoctionChinese herb medicinenetwork pharmacologygastric cancerAkt/ERK/p53 signaling pathwaysMCM2 |
| spellingShingle | Boyu Pan Yun Wang Chunnuan Wu Junrong Jia Chen Huang Senbiao Fang Liren Liu A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer Frontiers in Pharmacology Danggui Sini Decoction Chinese herb medicine network pharmacology gastric cancer Akt/ERK/p53 signaling pathways MCM2 |
| title | A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer |
| title_full | A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer |
| title_fullStr | A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer |
| title_full_unstemmed | A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer |
| title_short | A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer |
| title_sort | mechanism of action study on danggui sini decoction to discover its therapeutic effect on gastric cancer |
| topic | Danggui Sini Decoction Chinese herb medicine network pharmacology gastric cancer Akt/ERK/p53 signaling pathways MCM2 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.592903/full |
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