Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study
Siteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.671382/full |
| _version_ | 1818864305844518912 |
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| author | Lingjian Guo Haixia Shi Limin Zhu |
| author_facet | Lingjian Guo Haixia Shi Limin Zhu |
| author_sort | Lingjian Guo |
| collection | DOAJ |
| description | Siteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversing the MDR of GC. The chemical composition of STF and genes related to GC were obtained from the TCMNPAS(TCM Network Pharmacology Analysis System, TCMNPAS) Database, and the targets of the active ingredients were predicted using the Swiss Target Prediction Database. The obtained data were mapped to obtain the key active ingredients and core targets of STF in treating GC. The active component-target network and protein interaction network were constructed by Cytoscape and String database, and the key genes and core active ingredients were obtained. The biological functions and related signal pathways corresponding to the key targets were analyzed and then verified via molecular docking. A total of 14 core active ingredients of STF were screened, as well as 20 corresponding targets, which were mainly enriched in cancer pathway, proteoglycan synthesis, PI3K-AKT signaling pathway, and focal adhesion. Molecular docking showed that the core active ingredients related to MDR, namely quercetin and diosgenin, could bind well to the target. In summary, STF may reverse the MDR of GC and exert synergistic effect with chemotherapeutic drugs. It mediates MDR mainly through the action of quercetin and diosgenin on the PI3K/AKT signaling pathway. These findings are the first to demonstrate the molecular mechanism of STF in reversing MDR in GC, thus providing a direction for follow-up basic research. |
| first_indexed | 2024-12-19T10:29:33Z |
| format | Article |
| id | doaj.art-be19ac8af8264b1e9483f359b013d659 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-19T10:29:33Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-be19ac8af8264b1e9483f359b013d6592022-12-21T20:25:48ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.671382671382Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking StudyLingjian Guo0Haixia Shi1Limin Zhu2LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai Ninth People’s Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaLongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSiteng Fang (STF) has been shown to inhibit migration, invasion, and adhesion as well as promote apoptosis in gastric cancer (GC) cells. However, whether it can reverse the multidrug resistance (MDR) of GC to chemotherapy drugs is unknown. Thus, we aimed to elucidate the mechanism of STF in reversing the MDR of GC. The chemical composition of STF and genes related to GC were obtained from the TCMNPAS(TCM Network Pharmacology Analysis System, TCMNPAS) Database, and the targets of the active ingredients were predicted using the Swiss Target Prediction Database. The obtained data were mapped to obtain the key active ingredients and core targets of STF in treating GC. The active component-target network and protein interaction network were constructed by Cytoscape and String database, and the key genes and core active ingredients were obtained. The biological functions and related signal pathways corresponding to the key targets were analyzed and then verified via molecular docking. A total of 14 core active ingredients of STF were screened, as well as 20 corresponding targets, which were mainly enriched in cancer pathway, proteoglycan synthesis, PI3K-AKT signaling pathway, and focal adhesion. Molecular docking showed that the core active ingredients related to MDR, namely quercetin and diosgenin, could bind well to the target. In summary, STF may reverse the MDR of GC and exert synergistic effect with chemotherapeutic drugs. It mediates MDR mainly through the action of quercetin and diosgenin on the PI3K/AKT signaling pathway. These findings are the first to demonstrate the molecular mechanism of STF in reversing MDR in GC, thus providing a direction for follow-up basic research.https://www.frontiersin.org/articles/10.3389/fonc.2021.671382/fullSiteng Fanggastric cancernetwork pharmacologymolecular dockingmultidrug resistance |
| spellingShingle | Lingjian Guo Haixia Shi Limin Zhu Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study Frontiers in Oncology Siteng Fang gastric cancer network pharmacology molecular docking multidrug resistance |
| title | Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study |
| title_full | Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study |
| title_fullStr | Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study |
| title_full_unstemmed | Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study |
| title_short | Siteng Fang Reverses Multidrug Resistance in Gastric Cancer: A Network Pharmacology and Molecular Docking Study |
| title_sort | siteng fang reverses multidrug resistance in gastric cancer a network pharmacology and molecular docking study |
| topic | Siteng Fang gastric cancer network pharmacology molecular docking multidrug resistance |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.671382/full |
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