Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation
Shi-Han Feng,1,* Bin Zhao,1,* Xue Zhan,2 Retsepile Motanyane,2 Shu-Mei Wang,2 Ao Li3 1Yong Chuan Hospital of Chongqing Medical University, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Traditional Chinese Medicine,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-02-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/danggui-buxue-decoction-in-the-treatment-of-metastatic-colon-cancer-ne-peer-reviewed-article-DDDT |
| _version_ | 1828962436042981376 |
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| author | Feng SH Zhao B Zhan X Motanyane R Wang SM Li A |
| author_facet | Feng SH Zhao B Zhan X Motanyane R Wang SM Li A |
| author_sort | Feng SH |
| collection | DOAJ |
| description | Shi-Han Feng,1,* Bin Zhao,1,* Xue Zhan,2 Retsepile Motanyane,2 Shu-Mei Wang,2 Ao Li3 1Yong Chuan Hospital of Chongqing Medical University, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3Yong Chuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Mei WangCollege of Traditional Chinese Medicine, Chongqing Medical University, No. 1 Medical College Road, Chongqing, 400016, People’s Republic of ChinaTel +86-18716369329Email wangshumei@cqmu.edu.cnAo LiYong Chuan Hospital of Chongqing Medical University, NO. 439 Xuan Hua Road, Yongchuan District, Chongqing, 402160, People’s Republic of ChinaTel +86-18580779649Email wo_shi_li_ao_2@163.comPurpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.Keywords: Danggui Buxue Decoction, network pharmacology, primary tumor, metastatic tumor, perioperative period |
| first_indexed | 2024-12-14T10:04:04Z |
| format | Article |
| id | doaj.art-198ccb05e98e4cdab3a10436391c05b1 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-14T10:04:04Z |
| publishDate | 2021-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-198ccb05e98e4cdab3a10436391c05b12022-12-21T23:07:11ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-02-01Volume 1570572062442Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental ValidationFeng SHZhao BZhan XMotanyane RWang SMLi AShi-Han Feng,1,* Bin Zhao,1,* Xue Zhan,2 Retsepile Motanyane,2 Shu-Mei Wang,2 Ao Li3 1Yong Chuan Hospital of Chongqing Medical University, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People’s Republic of China; 3Yong Chuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Mei WangCollege of Traditional Chinese Medicine, Chongqing Medical University, No. 1 Medical College Road, Chongqing, 400016, People’s Republic of ChinaTel +86-18716369329Email wangshumei@cqmu.edu.cnAo LiYong Chuan Hospital of Chongqing Medical University, NO. 439 Xuan Hua Road, Yongchuan District, Chongqing, 402160, People’s Republic of ChinaTel +86-18580779649Email wo_shi_li_ao_2@163.comPurpose: This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.Results: A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.Conclusion: This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.Keywords: Danggui Buxue Decoction, network pharmacology, primary tumor, metastatic tumor, perioperative periodhttps://www.dovepress.com/danggui-buxue-decoction-in-the-treatment-of-metastatic-colon-cancer-ne-peer-reviewed-article-DDDTdanggui buxue decoctionnetwork pharmacologyprimary tumormetastatic tumorperioperative period |
| spellingShingle | Feng SH Zhao B Zhan X Motanyane R Wang SM Li A Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation Drug Design, Development and Therapy danggui buxue decoction network pharmacology primary tumor metastatic tumor perioperative period |
| title | Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
| title_full | Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
| title_fullStr | Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
| title_full_unstemmed | Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
| title_short | Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
| title_sort | danggui buxue decoction in the treatment of metastatic colon cancer network pharmacology analysis and experimental validation |
| topic | danggui buxue decoction network pharmacology primary tumor metastatic tumor perioperative period |
| url | https://www.dovepress.com/danggui-buxue-decoction-in-the-treatment-of-metastatic-colon-cancer-ne-peer-reviewed-article-DDDT |
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