Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic t...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2022-12, Vol.17 (12), p.e0279522-e0279522
Hauptverfasser: Choupani, Edris, Madjd, Zahra, Saraygord-Afshari, Neda, Kiani, Jafar, Hosseini, Arshad
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page e0279522
container_issue 12
container_start_page e0279522
container_title PloS one
container_volume 17
creator Choupani, Edris
Madjd, Zahra
Saraygord-Afshari, Neda
Kiani, Jafar
Hosseini, Arshad
description Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone.
doi_str_mv 10.1371/journal.pone.0279522
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2757027733</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A730926266</galeid><sourcerecordid>A730926266</sourcerecordid><originalsourceid>FETCH-LOGICAL-c626t-327ea38427b61151e80971bb4058e088b776f8e18f05403e367190d93bc3d13b3</originalsourceid><addsrcrecordid>eNqNkktr3DAQx01padK036C0gkJpD7vRw5bsSyFsX6GBQF9XIcnjtYItbSQ5fVz7xaslTtgtORQdNIx-MyP99S-KpwQvCRPk-MJPwalhufEOlpiKpqL0XnFIGkYXnGJ2fyc-KB7FeIFxxWrOHxYHjFdlzRg_LP6s_KitU8l6h3yHlGuDX4NDAQxskg_Iut5qu43A_VbDlNRoW0A_bOpR6gGt3n4qj_kOFqz2xprB6pxEKdjNAMjBOs-4AqQDqJiQUc5AQAaGIT4uHnRqiPBk3o-Kb-_ffV19XJydfzhdnZwtDKc8LRgVoFhdUqE5IRWBGjeCaF3iqgZc11oI3tVA6g5XJWbAuCANbhumDWsJ0-yoeH7ddzP4KGf9oqSiElk_wVgm3szEpEdoDbgU1CA3wY4q_JJeWbl_4mwv1_5KNkI0mNHc4NXcIPjLCWKSo43bRyoHfppnVbysq4y--Ae9-0YztVYDSOs6n-eabVN5IhhuaJaGZ2p5B5VXC6M12SCdzfm9gtd7BZlJ8DOt1RSjPP3y-f_Z8-_77Msdtgc1pD76bJpsr7gPltegCT7GAN2tyATLrb9v1JBbf8vZ37ns2e4H3RbdGJr9BV3Y9fo</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2757027733</pqid></control><display><type>article</type><title>Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Choupani, Edris ; Madjd, Zahra ; Saraygord-Afshari, Neda ; Kiani, Jafar ; Hosseini, Arshad</creator><contributor>Migliaccio, Antimo</contributor><creatorcontrib>Choupani, Edris ; Madjd, Zahra ; Saraygord-Afshari, Neda ; Kiani, Jafar ; Hosseini, Arshad ; Migliaccio, Antimo</creatorcontrib><description>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0279522</identifier><identifier>PMID: 36548336</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Androgen Receptor Antagonists - therapeutic use ; Androgen receptors ; Androgens ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biology and Life Sciences ; Breast cancer ; Cell cycle ; Cell Line, Tumor ; Cell migration ; Chemotherapy ; Chemotherapy, Combination ; Computer and Information Sciences ; Cyclin-dependent kinase 4 ; Cyclin-Dependent Kinase 4 - antagonists &amp; inhibitors ; Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors ; Cyclin-dependent kinases ; Engineering and Technology ; FDA approval ; Gene expression ; Humans ; Kinases ; Medical prognosis ; Medicine and Health Sciences ; Ontology ; Prostate cancer ; Protein Kinase Inhibitors - therapeutic use ; Proteins ; Receptors ; Receptors, Androgen - metabolism ; Research and Analysis Methods ; Targeted cancer therapy ; Therapeutic targets ; Triple Negative Breast Neoplasms - drug therapy</subject><ispartof>PloS one, 2022-12, Vol.17 (12), p.e0279522-e0279522</ispartof><rights>Copyright: © 2022 Choupani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Choupani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 Choupani et al 2022 Choupani et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c626t-327ea38427b61151e80971bb4058e088b776f8e18f05403e367190d93bc3d13b3</citedby><cites>FETCH-LOGICAL-c626t-327ea38427b61151e80971bb4058e088b776f8e18f05403e367190d93bc3d13b3</cites><orcidid>0000-0002-2077-0817</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779032/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779032/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36548336$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Migliaccio, Antimo</contributor><creatorcontrib>Choupani, Edris</creatorcontrib><creatorcontrib>Madjd, Zahra</creatorcontrib><creatorcontrib>Saraygord-Afshari, Neda</creatorcontrib><creatorcontrib>Kiani, Jafar</creatorcontrib><creatorcontrib>Hosseini, Arshad</creatorcontrib><title>Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone.</description><subject>Androgen Receptor Antagonists - therapeutic use</subject><subject>Androgen receptors</subject><subject>Androgens</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Combination</subject><subject>Computer and Information Sciences</subject><subject>Cyclin-dependent kinase 4</subject><subject>Cyclin-Dependent Kinase 4 - antagonists &amp; inhibitors</subject><subject>Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors</subject><subject>Cyclin-dependent kinases</subject><subject>Engineering and Technology</subject><subject>FDA approval</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Kinases</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Ontology</subject><subject>Prostate cancer</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Androgen - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Targeted cancer therapy</subject><subject>Therapeutic targets</subject><subject>Triple Negative Breast Neoplasms - drug therapy</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkktr3DAQx01padK036C0gkJpD7vRw5bsSyFsX6GBQF9XIcnjtYItbSQ5fVz7xaslTtgtORQdNIx-MyP99S-KpwQvCRPk-MJPwalhufEOlpiKpqL0XnFIGkYXnGJ2fyc-KB7FeIFxxWrOHxYHjFdlzRg_LP6s_KitU8l6h3yHlGuDX4NDAQxskg_Iut5qu43A_VbDlNRoW0A_bOpR6gGt3n4qj_kOFqz2xprB6pxEKdjNAMjBOs-4AqQDqJiQUc5AQAaGIT4uHnRqiPBk3o-Kb-_ffV19XJydfzhdnZwtDKc8LRgVoFhdUqE5IRWBGjeCaF3iqgZc11oI3tVA6g5XJWbAuCANbhumDWsJ0-yoeH7ddzP4KGf9oqSiElk_wVgm3szEpEdoDbgU1CA3wY4q_JJeWbl_4mwv1_5KNkI0mNHc4NXcIPjLCWKSo43bRyoHfppnVbysq4y--Ae9-0YztVYDSOs6n-eabVN5IhhuaJaGZ2p5B5VXC6M12SCdzfm9gtd7BZlJ8DOt1RSjPP3y-f_Z8-_77Msdtgc1pD76bJpsr7gPltegCT7GAN2tyATLrb9v1JBbf8vZ37ns2e4H3RbdGJr9BV3Y9fo</recordid><startdate>20221222</startdate><enddate>20221222</enddate><creator>Choupani, Edris</creator><creator>Madjd, Zahra</creator><creator>Saraygord-Afshari, Neda</creator><creator>Kiani, Jafar</creator><creator>Hosseini, Arshad</creator><general>Public Library of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2077-0817</orcidid></search><sort><creationdate>20221222</creationdate><title>Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells</title><author>Choupani, Edris ; Madjd, Zahra ; Saraygord-Afshari, Neda ; Kiani, Jafar ; Hosseini, Arshad</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c626t-327ea38427b61151e80971bb4058e088b776f8e18f05403e367190d93bc3d13b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Androgen Receptor Antagonists - therapeutic use</topic><topic>Androgen receptors</topic><topic>Androgens</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Chemotherapy</topic><topic>Chemotherapy, Combination</topic><topic>Computer and Information Sciences</topic><topic>Cyclin-dependent kinase 4</topic><topic>Cyclin-Dependent Kinase 4 - antagonists &amp; inhibitors</topic><topic>Cyclin-Dependent Kinase 6 - antagonists &amp; inhibitors</topic><topic>Cyclin-dependent kinases</topic><topic>Engineering and Technology</topic><topic>FDA approval</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Kinases</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Ontology</topic><topic>Prostate cancer</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Receptors, Androgen - metabolism</topic><topic>Research and Analysis Methods</topic><topic>Targeted cancer therapy</topic><topic>Therapeutic targets</topic><topic>Triple Negative Breast Neoplasms - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choupani, Edris</creatorcontrib><creatorcontrib>Madjd, Zahra</creatorcontrib><creatorcontrib>Saraygord-Afshari, Neda</creatorcontrib><creatorcontrib>Kiani, Jafar</creatorcontrib><creatorcontrib>Hosseini, Arshad</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choupani, Edris</au><au>Madjd, Zahra</au><au>Saraygord-Afshari, Neda</au><au>Kiani, Jafar</au><au>Hosseini, Arshad</au><au>Migliaccio, Antimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-12-22</date><risdate>2022</risdate><volume>17</volume><issue>12</issue><spage>e0279522</spage><epage>e0279522</epage><pages>e0279522-e0279522</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36548336</pmid><doi>10.1371/journal.pone.0279522</doi><tpages>e0279522</tpages><orcidid>https://orcid.org/0000-0002-2077-0817</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2022-12, Vol.17 (12), p.e0279522-e0279522
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_2757027733
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry
subjects Androgen Receptor Antagonists - therapeutic use
Androgen receptors
Androgens
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biology and Life Sciences
Breast cancer
Cell cycle
Cell Line, Tumor
Cell migration
Chemotherapy
Chemotherapy, Combination
Computer and Information Sciences
Cyclin-dependent kinase 4
Cyclin-Dependent Kinase 4 - antagonists & inhibitors
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
Cyclin-dependent kinases
Engineering and Technology
FDA approval
Gene expression
Humans
Kinases
Medical prognosis
Medicine and Health Sciences
Ontology
Prostate cancer
Protein Kinase Inhibitors - therapeutic use
Proteins
Receptors
Receptors, Androgen - metabolism
Research and Analysis Methods
Targeted cancer therapy
Therapeutic targets
Triple Negative Breast Neoplasms - drug therapy
title Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T22%3A16%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Combination%20of%20androgen%20receptor%20inhibitor%20enzalutamide%20with%20the%20CDK4/6%20inhibitor%20ribociclib%20in%20triple%20negative%20breast%20cancer%20cells&rft.jtitle=PloS%20one&rft.au=Choupani,%20Edris&rft.date=2022-12-22&rft.volume=17&rft.issue=12&rft.spage=e0279522&rft.epage=e0279522&rft.pages=e0279522-e0279522&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0279522&rft_dat=%3Cgale_plos_%3EA730926266%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2757027733&rft_id=info:pmid/36548336&rft_galeid=A730926266&rfr_iscdi=true