Cargando…
Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation
PURPOSE: 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 que...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917330/ https://www.ncbi.nlm.nih.gov/pubmed/33658761 http://dx.doi.org/10.2147/DDDT.S293046 |
_version_ | 1783657676520030208 |
---|---|
author | Feng, Shi-Han Zhao, Bin Zhan, Xue Motanyane, Retsepile Wang, Shu-Mei Li, Ao |
author_facet | Feng, Shi-Han Zhao, Bin Zhan, Xue Motanyane, Retsepile Wang, Shu-Mei Li, Ao |
author_sort | Feng, Shi-Han |
collection | PubMed |
description | PURPOSE: 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. |
format | Online Article Text |
id | pubmed-7917330 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-79173302021-03-02 Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation Feng, Shi-Han Zhao, Bin Zhan, Xue Motanyane, Retsepile Wang, Shu-Mei Li, Ao Drug Des Devel Ther Original Research PURPOSE: 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. Dove 2021-02-24 /pmc/articles/PMC7917330/ /pubmed/33658761 http://dx.doi.org/10.2147/DDDT.S293046 Text en © 2021 Feng et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Feng, Shi-Han Zhao, Bin Zhan, Xue Motanyane, Retsepile Wang, Shu-Mei Li, Ao Danggui Buxue Decoction in the Treatment of Metastatic Colon Cancer: Network Pharmacology Analysis and Experimental Validation |
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 | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917330/ https://www.ncbi.nlm.nih.gov/pubmed/33658761 http://dx.doi.org/10.2147/DDDT.S293046 |
work_keys_str_mv | AT fengshihan dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation AT zhaobin dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation AT zhanxue dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation AT motanyaneretsepile dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation AT wangshumei dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation AT liao dangguibuxuedecoctioninthetreatmentofmetastaticcoloncancernetworkpharmacologyanalysisandexperimentalvalidation |