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Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification
Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631906/ https://www.ncbi.nlm.nih.gov/pubmed/34858165 http://dx.doi.org/10.3389/fphar.2021.685773 |
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author | Zhang, Yubao Ma, Xiaoran Li, Huayao Zhuang, Jing Feng, Fubin Liu, Lijuan Liu, Cun Sun, Changgang |
author_facet | Zhang, Yubao Ma, Xiaoran Li, Huayao Zhuang, Jing Feng, Fubin Liu, Lijuan Liu, Cun Sun, Changgang |
author_sort | Zhang, Yubao |
collection | PubMed |
description | Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy. |
format | Online Article Text |
id | pubmed-8631906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86319062021-12-01 Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification Zhang, Yubao Ma, Xiaoran Li, Huayao Zhuang, Jing Feng, Fubin Liu, Lijuan Liu, Cun Sun, Changgang Front Pharmacol Pharmacology Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8631906/ /pubmed/34858165 http://dx.doi.org/10.3389/fphar.2021.685773 Text en Copyright © 2021 Zhang, Ma, Li, Zhuang, Feng, Liu, Liu and Sun. 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 | Pharmacology Zhang, Yubao Ma, Xiaoran Li, Huayao Zhuang, Jing Feng, Fubin Liu, Lijuan Liu, Cun Sun, Changgang Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title | Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title_full | Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title_fullStr | Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title_full_unstemmed | Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title_short | Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification |
title_sort | identifying the effect of ursolic acid against triple-negative breast cancer: coupling network pharmacology with experiments verification |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8631906/ https://www.ncbi.nlm.nih.gov/pubmed/34858165 http://dx.doi.org/10.3389/fphar.2021.685773 |
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