Hydroxychloroquine suppresses lung tumorigenesis via inducing FoxO3a nuclear translocation through STAT3 inactivation.
Identifieur interne : 000008 ( PubMed/Curation ); précédent : 000007; suivant : 000009Hydroxychloroquine suppresses lung tumorigenesis via inducing FoxO3a nuclear translocation through STAT3 inactivation.
Auteurs : Xin Lyu [République populaire de Chine] ; Lizhong Zeng [République populaire de Chine] ; Hua Zhang [République populaire de Chine] ; Yue Ke [République populaire de Chine] ; Xuan Liu [République populaire de Chine] ; Nannan Zhao [République populaire de Chine] ; Jingyan Yuan [République populaire de Chine] ; Guoan Chen [République populaire de Chine] ; Shuanying Yang [République populaire de Chine]Source :
- Life sciences [ 1879-0631 ] ; 2020.
Descripteurs français
- KwdFr :
- Adénocarcinome (métabolisme), Adénocarcinome (traitement médicamenteux), Animaux, Antinéoplasiques (usage thérapeutique), Apoptose (), Cellules A549, Cycle cellulaire (), Facteur de transcription STAT-3 (métabolisme), Femelle, Humains, Hydroxychloroquine (usage thérapeutique), Lignée cellulaire tumorale, Protéine O3 à motif en tête de fourche (métabolisme), Régulation de l'expression des gènes tumoraux (), Souris nude, Transplantation tumorale, Transport nucléaire actif (), Tumeurs du poumon (métabolisme), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- métabolisme : Adénocarcinome, Facteur de transcription STAT-3, Protéine O3 à motif en tête de fourche, Tumeurs du poumon.
- traitement médicamenteux : Adénocarcinome, Tumeurs du poumon.
- usage thérapeutique : Antinéoplasiques, Hydroxychloroquine.
- Animaux, Apoptose, Cellules A549, Cycle cellulaire, Femelle, Humains, Lignée cellulaire tumorale, Régulation de l'expression des gènes tumoraux, Souris nude, Transplantation tumorale, Transport nucléaire actif.
English descriptors
- KwdEn :
- A549 Cells, Active Transport, Cell Nucleus (drug effects), Adenocarcinoma (drug therapy), Adenocarcinoma (metabolism), Animals, Antineoplastic Agents (therapeutic use), Apoptosis (drug effects), Cell Cycle (drug effects), Cell Line, Tumor, Female, Forkhead Box Protein O3 (metabolism), Gene Expression Regulation, Neoplastic (drug effects), Humans, Hydroxychloroquine (therapeutic use), Lung Neoplasms (drug therapy), Lung Neoplasms (metabolism), Mice, Nude, Neoplasm Transplantation, STAT3 Transcription Factor (metabolism).
- MESH :
- chemical , metabolism : Forkhead Box Protein O3, STAT3 Transcription Factor.
- chemical , therapeutic use : Antineoplastic Agents, Hydroxychloroquine.
- drug effects : Active Transport, Cell Nucleus, Apoptosis, Cell Cycle, Gene Expression Regulation, Neoplastic.
- drug therapy : Adenocarcinoma, Lung Neoplasms.
- metabolism : Adenocarcinoma, Lung Neoplasms.
- A549 Cells, Animals, Cell Line, Tumor, Female, Humans, Mice, Nude, Neoplasm Transplantation.
Abstract
Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated.
DOI: 10.1016/j.lfs.2020.117366
PubMed: 32001266
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term>
<term>Active Transport, Cell Nucleus (drug effects)</term>
<term>Adenocarcinoma (drug therapy)</term>
<term>Adenocarcinoma (metabolism)</term>
<term>Animals</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Apoptosis (drug effects)</term>
<term>Cell Cycle (drug effects)</term>
<term>Cell Line, Tumor</term>
<term>Female</term>
<term>Forkhead Box Protein O3 (metabolism)</term>
<term>Gene Expression Regulation, Neoplastic (drug effects)</term>
<term>Humans</term>
<term>Hydroxychloroquine (therapeutic use)</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (metabolism)</term>
<term>Mice, Nude</term>
<term>Neoplasm Transplantation</term>
<term>STAT3 Transcription Factor (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adénocarcinome (métabolisme)</term>
<term>Adénocarcinome (traitement médicamenteux)</term>
<term>Animaux</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Apoptose ()</term>
<term>Cellules A549</term>
<term>Cycle cellulaire ()</term>
<term>Facteur de transcription STAT-3 (métabolisme)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Hydroxychloroquine (usage thérapeutique)</term>
<term>Lignée cellulaire tumorale</term>
<term>Protéine O3 à motif en tête de fourche (métabolisme)</term>
<term>Régulation de l'expression des gènes tumoraux ()</term>
<term>Souris nude</term>
<term>Transplantation tumorale</term>
<term>Transport nucléaire actif ()</term>
<term>Tumeurs du poumon (métabolisme)</term>
<term>Tumeurs du poumon (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Forkhead Box Protein O3</term>
<term>STAT3 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antineoplastic Agents</term>
<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Active Transport, Cell Nucleus</term>
<term>Apoptosis</term>
<term>Cell Cycle</term>
<term>Gene Expression Regulation, Neoplastic</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Adenocarcinoma</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Adenocarcinoma</term>
<term>Lung Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Adénocarcinome</term>
<term>Facteur de transcription STAT-3</term>
<term>Protéine O3 à motif en tête de fourche</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Adénocarcinome</term>
<term>Tumeurs du poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antinéoplasiques</term>
<term>Hydroxychloroquine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term>
<term>Animals</term>
<term>Cell Line, Tumor</term>
<term>Female</term>
<term>Humans</term>
<term>Mice, Nude</term>
<term>Neoplasm Transplantation</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Apoptose</term>
<term>Cellules A549</term>
<term>Cycle cellulaire</term>
<term>Femelle</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Régulation de l'expression des gènes tumoraux</term>
<term>Souris nude</term>
<term>Transplantation tumorale</term>
<term>Transport nucléaire actif</term>
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<front><div type="abstract" xml:lang="en">Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32001266</PMID>
<DateCompleted><Year>2020</Year>
<Month>03</Month>
<Day>23</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>23</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1879-0631</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>246</Volume>
<PubDate><Year>2020</Year>
<Month>Apr</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>Life sciences</Title>
<ISOAbbreviation>Life Sci.</ISOAbbreviation>
</Journal>
<ArticleTitle>Hydroxychloroquine suppresses lung tumorigenesis via inducing FoxO3a nuclear translocation through STAT3 inactivation.</ArticleTitle>
<Pagination><MedlinePgn>117366</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0024-3205(20)30113-2</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.lfs.2020.117366</ELocationID>
<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Hydroxychloroquine exhibits synergistic anticancer properties as an adjuvant. However, the role and molecular mechanisms underlying of HCQ as monotherapy for lung adenocarcinoma (LUAD) have yet to be elucidated.</AbstractText>
<AbstractText Label="METHODS" NlmCategory="METHODS">We assessed the antitumor effects of HCQ in LUAD cells through a series of in vitro and in vivo assays. GEO database and R packages were used to predict molecular mechanisms of HCQ in the treatment of lung adenocarcinoma, followed by verification of gene expression and subcellular localization via immunoblotting, immunofluorescent and immunohistochemistry assays.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">We showed the phenotypic effects that HCQ inhibited cell growth, induced apoptosis and cell cycle arrest at G1/S transition in A549 and PC-9 cells, which was associated with inhibition of CDK2, CDK4, CyclinD1 and CyclinE, but up-regulation of p21 and p27<sup>Kip1</sup>
. Bioinformatic analysis predicted that 63 targets related to HCQ and LUAD were mainly enriched in JAK-STAT and FoxO pathways. Then, we observed that HCQ decreased the phosphorylation of STAT3, but increased the expression of FoxO3a and its accumulation in the nucleus. The specific STAT3 inhibitor cryptotanshinon augmented the HCQ-induced upregulation and nuclear translocation of FoxO3a. In addition, HCQ increased the expression of p27<sup>Kip1</sup>
, which was impaired by FoxO3a blockade with siRNA. Finally, ablation of p27<sup>Kip1</sup>
expression abrogated the cytotoxicity of HCQ. More importantly, similar results were further confirmed in vivo.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Taken together, this study suggests that STAT3/FoxO3a/p27<sup>Kip1</sup>
signaling pathway is involved in the anticancer effects of HCQ, and provides preliminary evidence for therapeutic prospects of HCQ alone in LUAD.</AbstractText>
<CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lyu</LastName>
<ForeName>Xin</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zeng</LastName>
<ForeName>Lizhong</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhang</LastName>
<ForeName>Hua</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Department of Obstetrics and Gynecology, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ke</LastName>
<ForeName>Yue</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Radiation Oncology, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Xuan</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhao</LastName>
<ForeName>Nannan</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yuan</LastName>
<ForeName>Jingyan</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Guoan</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>School of Medicine, Southern University of Science and Technology, No. 1088, Xueyuan Road, Nanshan District, Shenzhen 518055, Guangdong, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Shuanying</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, PR China. Electronic address: yangshuangying66@163.com.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>01</Month>
<Day>28</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Netherlands</Country>
<MedlineTA>Life Sci</MedlineTA>
<NlmUniqueID>0375521</NlmUniqueID>
<ISSNLinking>0024-3205</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C499517">FOXO3 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000071316">Forkhead Box Protein O3</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D050796">STAT3 Transcription Factor</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C494086">STAT3 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber>
<NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000072283" MajorTopicYN="N">A549 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D021581" MajorTopicYN="N">Active Transport, Cell Nucleus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000230" MajorTopicYN="N">Adenocarcinoma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017209" MajorTopicYN="N">Apoptosis</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002453" MajorTopicYN="N">Cell Cycle</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000071316" MajorTopicYN="N">Forkhead Box Protein O3</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015972" MajorTopicYN="N">Gene Expression Regulation, Neoplastic</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008819" MajorTopicYN="N">Mice, Nude</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009368" MajorTopicYN="N">Neoplasm Transplantation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D050796" MajorTopicYN="N">STAT3 Transcription Factor</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Bioinformatic analysis</Keyword>
<Keyword MajorTopicYN="N">FoxO3a</Keyword>
<Keyword MajorTopicYN="N">Hydroxychloroquine</Keyword>
<Keyword MajorTopicYN="N">Lung adenocarcinoma</Keyword>
<Keyword MajorTopicYN="N">STAT3</Keyword>
<Keyword MajorTopicYN="N">p27(Kip1)</Keyword>
</KeywordList>
<CoiStatement>Declaration of competing interest The authors declare that there are no conflicts of interest.</CoiStatement>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year>
<Month>11</Month>
<Day>24</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2020</Year>
<Month>01</Month>
<Day>09</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="accepted"><Year>2020</Year>
<Month>01</Month>
<Day>26</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>2</Month>
<Day>1</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>3</Month>
<Day>24</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>2</Month>
<Day>1</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">32001266</ArticleId>
<ArticleId IdType="pii">S0024-3205(20)30113-2</ArticleId>
<ArticleId IdType="doi">10.1016/j.lfs.2020.117366</ArticleId>
</ArticleIdList>
</PubmedData>
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