The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology
Background: Resistance to chemotherapeutic drugs, such as oxaliplatin (OXA), can lead to unsatisfactory chemotherapy results during the treatment of advanced colorectal cancer (CRC). Therefore, we investigated the potential targets and mechanisms of Gegen Qinlian Decoction (GQD) against OXA-resistan...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022025932 |
| _version_ | 1798014482368167936 |
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| author | Xiang Lin Li Xu Huicheng Tan Xinyi Zhang Huan Shao Li Yao Xuan Huang |
| author_facet | Xiang Lin Li Xu Huicheng Tan Xinyi Zhang Huan Shao Li Yao Xuan Huang |
| author_sort | Xiang Lin |
| collection | DOAJ |
| description | Background: Resistance to chemotherapeutic drugs, such as oxaliplatin (OXA), can lead to unsatisfactory chemotherapy results during the treatment of advanced colorectal cancer (CRC). Therefore, we investigated the potential targets and mechanisms of Gegen Qinlian Decoction (GQD) against OXA-resistant CRC through network pharmacology and performed molecular docking and experimental verification. Methods: We collected potential compounds, targets, and related disease genes from public databases. The pharmacology model of the compound-target-pathway network and protein-protein interaction (PPI) network were established. The potential active components and mechanisms underlying GQD reversing OXA-resistant CRC were systematically predicted, and the key targets were verified by performing molecular docking and in vitro and in vivo experiments. Results: A total of 160 active ingredients, 407 potential targets, and 406 CRC drug resistance genes were collected. 16 intersecting genes, which included ABCG2 and belonged to 139 active compounds including baicalin and wogonin. They were enriched in 12 signaling pathways, including ABC transport and metabolism. Along with network topology analysis, ABCB1 and ABCC2 were identified as key targets and proved that various active components of GQD combined well with them. GQD alone and synergized with OXA could inhibit the protein and mRNA of ABC transporters in vivo and in vitro, decrease the IC50 of OXA-resistant CRC to OXA with a good synergistic index at different treatment times and concentrations, improve the sensitivity of OXA-resistant CRC to OXA, inhibit drug efflux, decrease tumor volume, and increase the weight of nude mice at the late stage of treatment. Conclusions: GQD can target ATP-binding proteins, inhibit ABC transporters, reverse OXA resistance, increase the sensitivity of OXA-resistant CRC cells to OXA, decrease tumor volume, alleviate toxic side effects, improve prognosis, and have good synergistic therapeutic effects. These results provide an effective research tool to elucidate ethnomedicine for modernizing refractory diseases. |
| first_indexed | 2024-04-11T15:19:05Z |
| format | Article |
| id | doaj.art-45001a46186c4cad959e30c1ed1390c2 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-11T15:19:05Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-45001a46186c4cad959e30c1ed1390c22022-12-22T04:16:25ZengElsevierHeliyon2405-84402022-11-01811e11305The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacologyXiang Lin0Li Xu1Huicheng Tan2Xinyi Zhang3Huan Shao4Li Yao5Xuan Huang6Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaCorresponding author.; Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, ChinaBackground: Resistance to chemotherapeutic drugs, such as oxaliplatin (OXA), can lead to unsatisfactory chemotherapy results during the treatment of advanced colorectal cancer (CRC). Therefore, we investigated the potential targets and mechanisms of Gegen Qinlian Decoction (GQD) against OXA-resistant CRC through network pharmacology and performed molecular docking and experimental verification. Methods: We collected potential compounds, targets, and related disease genes from public databases. The pharmacology model of the compound-target-pathway network and protein-protein interaction (PPI) network were established. The potential active components and mechanisms underlying GQD reversing OXA-resistant CRC were systematically predicted, and the key targets were verified by performing molecular docking and in vitro and in vivo experiments. Results: A total of 160 active ingredients, 407 potential targets, and 406 CRC drug resistance genes were collected. 16 intersecting genes, which included ABCG2 and belonged to 139 active compounds including baicalin and wogonin. They were enriched in 12 signaling pathways, including ABC transport and metabolism. Along with network topology analysis, ABCB1 and ABCC2 were identified as key targets and proved that various active components of GQD combined well with them. GQD alone and synergized with OXA could inhibit the protein and mRNA of ABC transporters in vivo and in vitro, decrease the IC50 of OXA-resistant CRC to OXA with a good synergistic index at different treatment times and concentrations, improve the sensitivity of OXA-resistant CRC to OXA, inhibit drug efflux, decrease tumor volume, and increase the weight of nude mice at the late stage of treatment. Conclusions: GQD can target ATP-binding proteins, inhibit ABC transporters, reverse OXA resistance, increase the sensitivity of OXA-resistant CRC cells to OXA, decrease tumor volume, alleviate toxic side effects, improve prognosis, and have good synergistic therapeutic effects. These results provide an effective research tool to elucidate ethnomedicine for modernizing refractory diseases.http://www.sciencedirect.com/science/article/pii/S2405844022025932Colorectal cancerGegen qinlian decoctionChemotherapy resistanceNetwork pharmacologyABC transporter |
| spellingShingle | Xiang Lin Li Xu Huicheng Tan Xinyi Zhang Huan Shao Li Yao Xuan Huang The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology Heliyon Colorectal cancer Gegen qinlian decoction Chemotherapy resistance Network pharmacology ABC transporter |
| title | The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology |
| title_full | The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology |
| title_fullStr | The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology |
| title_full_unstemmed | The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology |
| title_short | The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology |
| title_sort | potential effects and mechanisms of gegen qinlian decoction in oxaliplatin resistant colorectal cancer based on network pharmacology |
| topic | Colorectal cancer Gegen qinlian decoction Chemotherapy resistance Network pharmacology ABC transporter |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022025932 |
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