Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer
Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum‐based chemotherapy are still the standard care currently. However, resistance invoked often compromises...
Gespeichert in:
| Veröffentlicht in: | Cell biochemistry and function 2017-08, Vol.35 (6), p.296-303 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 303 |
|---|---|
| container_issue | 6 |
| container_start_page | 296 |
| container_title | Cell biochemistry and function |
| container_volume | 35 |
| creator | Cao, Ya‐Lei Zhuang, Ting Xing, Bao‐Heng Li, Na Li, Qin |
| description | Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum‐based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V‐PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co‐incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1‐containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients. |
| doi_str_mv | 10.1002/cbf.3276 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1927595382</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1932694739</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3496-75cc495a3488f3505a63a1bc85444733de8322678fbf0c63f57bea1fcedf04e23</originalsourceid><addsrcrecordid>eNp1kMtKAzEUQIMotlbBL5ABN26m5jV5bAStrQpVN3UdMmkCU-ZRkxm1f2_GVgXBVbjhcO7lAHCK4BhBiC9N7sYEc7YHhghKmUJB6T4YQsxIyqigA3AUwgpCKBmBh2CABZeIQzEEV9OPJjSVLpPbp8cFSiq7LHRrQ2KKsC51W9SJt6EIra6NTeLUvGlf6Dox_Yc_BgdOl8Ge7N4ReJlNF5P7dP589zC5nqeGUMlSnhlDZaYJFcKRDGaaEY1yIzJKKSdkaQXBmHHhcgcNIy7judXIGbt0kFpMRuBi61375rWzoVVVEYwtS13bpgsKScwzmRHRo-d_0FXT-TpeFymCmYwL5a_Q-CYEb51a-6LSfqMQVH1TFZuqvmlEz3bCLo95fsDviBFIt8B7UdrNvyI1uZl9CT8BLZV9nw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1932694739</pqid></control><display><type>article</type><title>Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Cao, Ya‐Lei ; Zhuang, Ting ; Xing, Bao‐Heng ; Li, Na ; Li, Qin</creator><creatorcontrib>Cao, Ya‐Lei ; Zhuang, Ting ; Xing, Bao‐Heng ; Li, Na ; Li, Qin</creatorcontrib><description>Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum‐based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V‐PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co‐incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1‐containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients.</description><identifier>ISSN: 0263-6484</identifier><identifier>EISSN: 1099-0844</identifier><identifier>DOI: 10.1002/cbf.3276</identifier><identifier>PMID: 28791708</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Aniline Compounds - pharmacology ; Animals ; Annexin V ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Apoptosis ; Benzylidene Compounds - pharmacology ; Biocompatibility ; Cancer ; Cell Line, Tumor ; Cell proliferation ; Cell Proliferation - drug effects ; Chemotherapy ; Cisplatin ; Cisplatin - therapeutic use ; Cisplatin - toxicity ; Conditioning ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA (Cytosine-5-)-Methyltransferases - metabolism ; DNA methyltransferase ; DNA methyltransferase 1 (DNMT1) ; DNMT1 protein ; Drug Resistance, Neoplasm - drug effects ; exosome ; Exosomes ; Exosomes - enzymology ; Female ; Gene expression ; Humans ; Immunoblotting ; Inhibitors ; Malignancy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Platinum ; Protein arrays ; resistance ; RNA, Messenger - metabolism ; Staining ; Surgery ; Survival ; Toxicity ; Transplantation, Heterologous ; Tumors ; Up-Regulation - drug effects ; Xenografts</subject><ispartof>Cell biochemistry and function, 2017-08, Vol.35 (6), p.296-303</ispartof><rights>Copyright © 2017 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3496-75cc495a3488f3505a63a1bc85444733de8322678fbf0c63f57bea1fcedf04e23</citedby><cites>FETCH-LOGICAL-c3496-75cc495a3488f3505a63a1bc85444733de8322678fbf0c63f57bea1fcedf04e23</cites><orcidid>0000-0002-8327-9769</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcbf.3276$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcbf.3276$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27926,27927,45576,45577</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28791708$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Ya‐Lei</creatorcontrib><creatorcontrib>Zhuang, Ting</creatorcontrib><creatorcontrib>Xing, Bao‐Heng</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Li, Qin</creatorcontrib><title>Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer</title><title>Cell biochemistry and function</title><addtitle>Cell Biochem Funct</addtitle><description>Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum‐based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V‐PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co‐incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1‐containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients.</description><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Annexin V</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Apoptosis</subject><subject>Benzylidene Compounds - pharmacology</subject><subject>Biocompatibility</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - therapeutic use</subject><subject>Cisplatin - toxicity</subject><subject>Conditioning</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - metabolism</subject><subject>DNA methyltransferase</subject><subject>DNA methyltransferase 1 (DNMT1)</subject><subject>DNMT1 protein</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>exosome</subject><subject>Exosomes</subject><subject>Exosomes - enzymology</subject><subject>Female</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Inhibitors</subject><subject>Malignancy</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Platinum</subject><subject>Protein arrays</subject><subject>resistance</subject><subject>RNA, Messenger - metabolism</subject><subject>Staining</subject><subject>Surgery</subject><subject>Survival</subject><subject>Toxicity</subject><subject>Transplantation, Heterologous</subject><subject>Tumors</subject><subject>Up-Regulation - drug effects</subject><subject>Xenografts</subject><issn>0263-6484</issn><issn>1099-0844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKAzEUQIMotlbBL5ABN26m5jV5bAStrQpVN3UdMmkCU-ZRkxm1f2_GVgXBVbjhcO7lAHCK4BhBiC9N7sYEc7YHhghKmUJB6T4YQsxIyqigA3AUwgpCKBmBh2CABZeIQzEEV9OPJjSVLpPbp8cFSiq7LHRrQ2KKsC51W9SJt6EIra6NTeLUvGlf6Dox_Yc_BgdOl8Ge7N4ReJlNF5P7dP589zC5nqeGUMlSnhlDZaYJFcKRDGaaEY1yIzJKKSdkaQXBmHHhcgcNIy7judXIGbt0kFpMRuBi61375rWzoVVVEYwtS13bpgsKScwzmRHRo-d_0FXT-TpeFymCmYwL5a_Q-CYEb51a-6LSfqMQVH1TFZuqvmlEz3bCLo95fsDviBFIt8B7UdrNvyI1uZl9CT8BLZV9nw</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Cao, Ya‐Lei</creator><creator>Zhuang, Ting</creator><creator>Xing, Bao‐Heng</creator><creator>Li, Na</creator><creator>Li, Qin</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8327-9769</orcidid></search><sort><creationdate>201708</creationdate><title>Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer</title><author>Cao, Ya‐Lei ; Zhuang, Ting ; Xing, Bao‐Heng ; Li, Na ; Li, Qin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3496-75cc495a3488f3505a63a1bc85444733de8322678fbf0c63f57bea1fcedf04e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Annexin V</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Apoptosis</topic><topic>Benzylidene Compounds - pharmacology</topic><topic>Biocompatibility</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Cisplatin - therapeutic use</topic><topic>Cisplatin - toxicity</topic><topic>Conditioning</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - metabolism</topic><topic>DNA methyltransferase</topic><topic>DNA methyltransferase 1 (DNMT1)</topic><topic>DNMT1 protein</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>exosome</topic><topic>Exosomes</topic><topic>Exosomes - enzymology</topic><topic>Female</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Inhibitors</topic><topic>Malignancy</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Platinum</topic><topic>Protein arrays</topic><topic>resistance</topic><topic>RNA, Messenger - metabolism</topic><topic>Staining</topic><topic>Surgery</topic><topic>Survival</topic><topic>Toxicity</topic><topic>Transplantation, Heterologous</topic><topic>Tumors</topic><topic>Up-Regulation - drug effects</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Ya‐Lei</creatorcontrib><creatorcontrib>Zhuang, Ting</creatorcontrib><creatorcontrib>Xing, Bao‐Heng</creatorcontrib><creatorcontrib>Li, Na</creatorcontrib><creatorcontrib>Li, Qin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell biochemistry and function</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Ya‐Lei</au><au>Zhuang, Ting</au><au>Xing, Bao‐Heng</au><au>Li, Na</au><au>Li, Qin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer</atitle><jtitle>Cell biochemistry and function</jtitle><addtitle>Cell Biochem Funct</addtitle><date>2017-08</date><risdate>2017</risdate><volume>35</volume><issue>6</issue><spage>296</spage><epage>303</epage><pages>296-303</pages><issn>0263-6484</issn><eissn>1099-0844</eissn><abstract>Ovarian cancer is the most common malignancy in women. Owing to late syndromic presentation and lack of efficient early detection, most cases are diagnosed at advanced stages. Surgery and platinum‐based chemotherapy are still the standard care currently. However, resistance invoked often compromises the clinical value of the latter. Expression of DNA methyltransferase 1 (DNMT1) was analysed by gene array. Protein was determined by immunoblotting. Exosome was isolated with commercial kit. Cell proliferation was measured by CCK8 method. Annexin V‐PI double staining was performed for apoptosis evaluation. Xenograft model was established and administrated with exosome. Tumour growth and overall survival were monitored. We demonstrated the upregulation of DNMT1 in both tumour and derived cell line. DNMT1 transcripts were highly enriched in exosomes from conditioned medium of ovarian cells. Co‐incubation with exosomes stimulated endogenous expression and rendered host cell the resistance to cytotoxicity of cisplatin. In vivo administration of DNMT1‐containing exosomes exacerbated xenograft progression and reduced overall survival significantly. Moreover, treatment with exosome inhibitor GW4869 almost completely restored sensitivity in resistant cells. Our data elucidated an unappreciated mechanism of exosomal DNMT1 in cisplatin resistance in ovarian cancer, also indicating the potential of the combination of exosome inhibitor with cisplatin in resistant patients.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28791708</pmid><doi>10.1002/cbf.3276</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-8327-9769</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0263-6484 |
| ispartof | Cell biochemistry and function, 2017-08, Vol.35 (6), p.296-303 |
| issn | 0263-6484 1099-0844 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1927595382 |
| source | MEDLINE; Access via Wiley Online Library |
| subjects | Aniline Compounds - pharmacology Animals Annexin V Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Apoptosis Benzylidene Compounds - pharmacology Biocompatibility Cancer Cell Line, Tumor Cell proliferation Cell Proliferation - drug effects Chemotherapy Cisplatin Cisplatin - therapeutic use Cisplatin - toxicity Conditioning Cytotoxicity Deoxyribonucleic acid DNA DNA (Cytosine-5-)-Methyltransferase 1 DNA (Cytosine-5-)-Methyltransferases - genetics DNA (Cytosine-5-)-Methyltransferases - metabolism DNA methyltransferase DNA methyltransferase 1 (DNMT1) DNMT1 protein Drug Resistance, Neoplasm - drug effects exosome Exosomes Exosomes - enzymology Female Gene expression Humans Immunoblotting Inhibitors Malignancy Mice Mice, Inbred BALB C Mice, Nude Ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Platinum Protein arrays resistance RNA, Messenger - metabolism Staining Surgery Survival Toxicity Transplantation, Heterologous Tumors Up-Regulation - drug effects Xenografts |
| title | Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T02%3A06%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exosomal%20DNMT1%20mediates%20cisplatin%20resistance%20in%20ovarian%20cancer&rft.jtitle=Cell%20biochemistry%20and%20function&rft.au=Cao,%20Ya%E2%80%90Lei&rft.date=2017-08&rft.volume=35&rft.issue=6&rft.spage=296&rft.epage=303&rft.pages=296-303&rft.issn=0263-6484&rft.eissn=1099-0844&rft_id=info:doi/10.1002/cbf.3276&rft_dat=%3Cproquest_cross%3E1932694739%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1932694739&rft_id=info:pmid/28791708&rfr_iscdi=true |