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Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database
BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the und...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396298/ https://www.ncbi.nlm.nih.gov/pubmed/36016606 http://dx.doi.org/10.3389/fonc.2022.946758 |
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author | Ye, Yong Zhang, Bo Liang, Qiuyun Wang, Dandan Bai, Facheng Li, Yuanhong Wei, Lizhi Li, Lilan Huang, Huixue Tang, Yunxia |
author_facet | Ye, Yong Zhang, Bo Liang, Qiuyun Wang, Dandan Bai, Facheng Li, Yuanhong Wei, Lizhi Li, Lilan Huang, Huixue Tang, Yunxia |
author_sort | Ye, Yong |
collection | PubMed |
description | BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the underlying mechanism remains unclear and needs to be fully elucidated. METHODS: The active constituents of CKI were identified through a literature review, and the anti-BC targets of CKI were determined using multiple databases and a ChIP data analysis. Subsequently, the target was analyzed on the DAVID database through GO and KEGG to identify the key pathway that CKI affects to exhibit anti-BC activity. In addition, MCF-7 and MDA-MB-231 cells were treated with CKI for 24 and 48 hours at five concentrations, and the effects of CKI on cell proliferation and apoptosis were measured using MTT and annexin V/propidium iodide staining assays, respectively. The genes and protein identified to be involved in this pathway were verified using real-time quantitative PCR (qPCR) and western blot(WB) in BC cells. RESULTS: Twelve CKI anti-BC targets were obtained by a comprehensive analysis of the targets collected in the databases and results from the ChIP analysis. Bioinformatics analysis was performed for 12 targets. KEGG analysis showed that the 12 targets were mainly related to the VEGF, ErbB, and TNF signaling pathways. We focused our study on the VEGF signaling pathway as the p-value for the VEGF signaling pathway was the lowest among the three pathways. In vitro experiments showed that CKI significantly inhibited the proliferation of BC cells and induced apoptosis. Furthermore, qPCR and WB experiments showed that the expression of VEGF signaling pathway genes PIK3CA and NOS3 were significantly increased meanwhile SRC was significantly decreased after CKI intervention. CONCLUSION: CKI significantly inhibited the proliferation of BC cells and induced apoptosis. The main mechanism for the anti-BC effect of CKI may be that it regulates the VEGF signaling pathway by increasing the expression of PIK3CA, SRC, and NOS3. Macrozamin and lamprolobine may be the main active components of CKI against BC. |
format | Online Article Text |
id | pubmed-9396298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93962982022-08-24 Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database Ye, Yong Zhang, Bo Liang, Qiuyun Wang, Dandan Bai, Facheng Li, Yuanhong Wei, Lizhi Li, Lilan Huang, Huixue Tang, Yunxia Front Oncol Oncology BACKGROUND: Breast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the underlying mechanism remains unclear and needs to be fully elucidated. METHODS: The active constituents of CKI were identified through a literature review, and the anti-BC targets of CKI were determined using multiple databases and a ChIP data analysis. Subsequently, the target was analyzed on the DAVID database through GO and KEGG to identify the key pathway that CKI affects to exhibit anti-BC activity. In addition, MCF-7 and MDA-MB-231 cells were treated with CKI for 24 and 48 hours at five concentrations, and the effects of CKI on cell proliferation and apoptosis were measured using MTT and annexin V/propidium iodide staining assays, respectively. The genes and protein identified to be involved in this pathway were verified using real-time quantitative PCR (qPCR) and western blot(WB) in BC cells. RESULTS: Twelve CKI anti-BC targets were obtained by a comprehensive analysis of the targets collected in the databases and results from the ChIP analysis. Bioinformatics analysis was performed for 12 targets. KEGG analysis showed that the 12 targets were mainly related to the VEGF, ErbB, and TNF signaling pathways. We focused our study on the VEGF signaling pathway as the p-value for the VEGF signaling pathway was the lowest among the three pathways. In vitro experiments showed that CKI significantly inhibited the proliferation of BC cells and induced apoptosis. Furthermore, qPCR and WB experiments showed that the expression of VEGF signaling pathway genes PIK3CA and NOS3 were significantly increased meanwhile SRC was significantly decreased after CKI intervention. CONCLUSION: CKI significantly inhibited the proliferation of BC cells and induced apoptosis. The main mechanism for the anti-BC effect of CKI may be that it regulates the VEGF signaling pathway by increasing the expression of PIK3CA, SRC, and NOS3. Macrozamin and lamprolobine may be the main active components of CKI against BC. Frontiers Media S.A. 2022-08-09 /pmc/articles/PMC9396298/ /pubmed/36016606 http://dx.doi.org/10.3389/fonc.2022.946758 Text en Copyright © 2022 Ye, Zhang, Liang, Wang, Bai, Li, Wei, Li, Huang and Tang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Ye, Yong Zhang, Bo Liang, Qiuyun Wang, Dandan Bai, Facheng Li, Yuanhong Wei, Lizhi Li, Lilan Huang, Huixue Tang, Yunxia Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title | Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title_full | Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title_fullStr | Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title_full_unstemmed | Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title_short | Exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: Coupling network pharmacology with GEO database |
title_sort | exploring the pharmacological mechanism of compound kushen injection in the treatment of breast cancer using in vitro experiments: coupling network pharmacology with geo database |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396298/ https://www.ncbi.nlm.nih.gov/pubmed/36016606 http://dx.doi.org/10.3389/fonc.2022.946758 |
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