Role of mTOR inhibitor in cholangiocarcinoma cell progression
Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (evero...
Gespeichert in:
| Veröffentlicht in: | Oncology letters 2014-03, Vol.7 (3), p.854-860 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 860 |
|---|---|
| container_issue | 3 |
| container_start_page | 854 |
| container_title | Oncology letters |
| container_volume | 7 |
| creator | MOOLTHIYA, PENPAK TOHTONG, RUTAIWAN KEERATICHAMROEN, SIRIPORN LEELAWAT, KAWIN |
| description | Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (everolimus), a derivative of rapamycin and an orally bioavailable mammalian target of rapamycin (mTOR) inhibitor, exhibits cytotoxic and antimetastatic effects in a CCA cell line, RMCCA-1. Treatment with low concentrations of RAD001 resulted in a significant reduction of in vitro invasion and migration of RMCCA-1, concomitant with a reduction of filopodia and alteration of the actin cytoskeleton. Although, matrix metalloproteinase-9 and -14 activities were unaltered. However, at high concentrations, RAD001 exhibited cytotoxic effects, reducing cell proliferation and inducing apoptotic cell death. Overall, RAD001 exhibits multiple effects mediated by the inhibition of the mTOR, which may serve as a promising agent for the treatment of CCA. |
| doi_str_mv | 10.3892/ol.2014.1799 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3919862</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A426827950</galeid><sourcerecordid>A426827950</sourcerecordid><originalsourceid>FETCH-LOGICAL-c541t-32fd127ca809e7b4aa50ad99bb48ffe2a57453d2c89450c642d4b8f8495e2c013</originalsourceid><addsrcrecordid>eNptkk1r3DAQhk1paUKaW8_FUCg91Ft9WtKhgRD6BYFASM9CluW1gqzZSnah_74ySTe7pdJhBumZGeblrarXGG2oVOQjhA1BmG2wUOpZdVoCaTCS5Pk-F-ykOs_5HpXDWyxl-7I6IYwTgRQ9rT7dQnA1DPV0d3Nb-zj6zs-QSlbbEYKJWw_WJOsjTKa2LoR6l2CbXM4e4qvqxWBCdueP8az68eXz3dW35vrm6_ery-vGcobnhpKhx0RYI5FyomPGcGR6pbqOyWFwxHDBOO2JlYpxZFtGetbJQTLFHbEI07Pq4qHvbukm11sX52SC3iU_mfRbg_H6-Cf6UW_hl6YKK9mS0uD9Y4MEPxeXZz35vG5jooMlayxJyyVHmBf07T_oPSwplvU0VpS0VApxQG1NcNrHAcpcuzbVl4y0kgjFUaE2_6HK7d3kLUQ3-PJ-VPDuoGB0JsxjhrDMRex8DH54AG2CnJMb9mJgpFdraAh6tYZerVHwN4cC7uG_RnganHcm9r6H_KRuaJBoEG2Q5Iz-AWdUvc4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1932638775</pqid></control><display><type>article</type><title>Role of mTOR inhibitor in cholangiocarcinoma cell progression</title><source>Spandidos Publications Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>MOOLTHIYA, PENPAK ; TOHTONG, RUTAIWAN ; KEERATICHAMROEN, SIRIPORN ; LEELAWAT, KAWIN</creator><creatorcontrib>MOOLTHIYA, PENPAK ; TOHTONG, RUTAIWAN ; KEERATICHAMROEN, SIRIPORN ; LEELAWAT, KAWIN</creatorcontrib><description>Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (everolimus), a derivative of rapamycin and an orally bioavailable mammalian target of rapamycin (mTOR) inhibitor, exhibits cytotoxic and antimetastatic effects in a CCA cell line, RMCCA-1. Treatment with low concentrations of RAD001 resulted in a significant reduction of in vitro invasion and migration of RMCCA-1, concomitant with a reduction of filopodia and alteration of the actin cytoskeleton. Although, matrix metalloproteinase-9 and -14 activities were unaltered. However, at high concentrations, RAD001 exhibited cytotoxic effects, reducing cell proliferation and inducing apoptotic cell death. Overall, RAD001 exhibits multiple effects mediated by the inhibition of the mTOR, which may serve as a promising agent for the treatment of CCA.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2014.1799</identifier><identifier>PMID: 24527093</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Cancer therapies ; Cell cycle ; Cell growth ; Cholangiocarcinoma ; Health aspects ; Kinases ; mTOR inhibitor ; Oncology ; Phosphorylation ; Phosphotransferases ; Proteins ; RAD001 ; Studies</subject><ispartof>Oncology letters, 2014-03, Vol.7 (3), p.854-860</ispartof><rights>Copyright © 2014, Spandidos Publications</rights><rights>COPYRIGHT 2014 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2014</rights><rights>Copyright © 2014, Spandidos Publications 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-32fd127ca809e7b4aa50ad99bb48ffe2a57453d2c89450c642d4b8f8495e2c013</citedby><cites>FETCH-LOGICAL-c541t-32fd127ca809e7b4aa50ad99bb48ffe2a57453d2c89450c642d4b8f8495e2c013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919862/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919862/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,5572,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24527093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MOOLTHIYA, PENPAK</creatorcontrib><creatorcontrib>TOHTONG, RUTAIWAN</creatorcontrib><creatorcontrib>KEERATICHAMROEN, SIRIPORN</creatorcontrib><creatorcontrib>LEELAWAT, KAWIN</creatorcontrib><title>Role of mTOR inhibitor in cholangiocarcinoma cell progression</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (everolimus), a derivative of rapamycin and an orally bioavailable mammalian target of rapamycin (mTOR) inhibitor, exhibits cytotoxic and antimetastatic effects in a CCA cell line, RMCCA-1. Treatment with low concentrations of RAD001 resulted in a significant reduction of in vitro invasion and migration of RMCCA-1, concomitant with a reduction of filopodia and alteration of the actin cytoskeleton. Although, matrix metalloproteinase-9 and -14 activities were unaltered. However, at high concentrations, RAD001 exhibited cytotoxic effects, reducing cell proliferation and inducing apoptotic cell death. Overall, RAD001 exhibits multiple effects mediated by the inhibition of the mTOR, which may serve as a promising agent for the treatment of CCA.</description><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cholangiocarcinoma</subject><subject>Health aspects</subject><subject>Kinases</subject><subject>mTOR inhibitor</subject><subject>Oncology</subject><subject>Phosphorylation</subject><subject>Phosphotransferases</subject><subject>Proteins</subject><subject>RAD001</subject><subject>Studies</subject><issn>1792-1074</issn><issn>1792-1082</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1r3DAQhk1paUKaW8_FUCg91Ft9WtKhgRD6BYFASM9CluW1gqzZSnah_74ySTe7pdJhBumZGeblrarXGG2oVOQjhA1BmG2wUOpZdVoCaTCS5Pk-F-ykOs_5HpXDWyxl-7I6IYwTgRQ9rT7dQnA1DPV0d3Nb-zj6zs-QSlbbEYKJWw_WJOsjTKa2LoR6l2CbXM4e4qvqxWBCdueP8az68eXz3dW35vrm6_ery-vGcobnhpKhx0RYI5FyomPGcGR6pbqOyWFwxHDBOO2JlYpxZFtGetbJQTLFHbEI07Pq4qHvbukm11sX52SC3iU_mfRbg_H6-Cf6UW_hl6YKK9mS0uD9Y4MEPxeXZz35vG5jooMlayxJyyVHmBf07T_oPSwplvU0VpS0VApxQG1NcNrHAcpcuzbVl4y0kgjFUaE2_6HK7d3kLUQ3-PJ-VPDuoGB0JsxjhrDMRex8DH54AG2CnJMb9mJgpFdraAh6tYZerVHwN4cC7uG_RnganHcm9r6H_KRuaJBoEG2Q5Iz-AWdUvc4</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>MOOLTHIYA, PENPAK</creator><creator>TOHTONG, RUTAIWAN</creator><creator>KEERATICHAMROEN, SIRIPORN</creator><creator>LEELAWAT, KAWIN</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140301</creationdate><title>Role of mTOR inhibitor in cholangiocarcinoma cell progression</title><author>MOOLTHIYA, PENPAK ; TOHTONG, RUTAIWAN ; KEERATICHAMROEN, SIRIPORN ; LEELAWAT, KAWIN</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-32fd127ca809e7b4aa50ad99bb48ffe2a57453d2c89450c642d4b8f8495e2c013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>Cholangiocarcinoma</topic><topic>Health aspects</topic><topic>Kinases</topic><topic>mTOR inhibitor</topic><topic>Oncology</topic><topic>Phosphorylation</topic><topic>Phosphotransferases</topic><topic>Proteins</topic><topic>RAD001</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MOOLTHIYA, PENPAK</creatorcontrib><creatorcontrib>TOHTONG, RUTAIWAN</creatorcontrib><creatorcontrib>KEERATICHAMROEN, SIRIPORN</creatorcontrib><creatorcontrib>LEELAWAT, KAWIN</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MOOLTHIYA, PENPAK</au><au>TOHTONG, RUTAIWAN</au><au>KEERATICHAMROEN, SIRIPORN</au><au>LEELAWAT, KAWIN</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of mTOR inhibitor in cholangiocarcinoma cell progression</atitle><jtitle>Oncology letters</jtitle><addtitle>Oncol Lett</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>7</volume><issue>3</issue><spage>854</spage><epage>860</epage><pages>854-860</pages><issn>1792-1074</issn><eissn>1792-1082</eissn><abstract>Cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium. CCA is resistant to currently available chemotherapy; therefore, new drugs as well as new molecular targets must be identified for the development of an effective treatment for CCA. The present study showed that RAD001 (everolimus), a derivative of rapamycin and an orally bioavailable mammalian target of rapamycin (mTOR) inhibitor, exhibits cytotoxic and antimetastatic effects in a CCA cell line, RMCCA-1. Treatment with low concentrations of RAD001 resulted in a significant reduction of in vitro invasion and migration of RMCCA-1, concomitant with a reduction of filopodia and alteration of the actin cytoskeleton. Although, matrix metalloproteinase-9 and -14 activities were unaltered. However, at high concentrations, RAD001 exhibited cytotoxic effects, reducing cell proliferation and inducing apoptotic cell death. Overall, RAD001 exhibits multiple effects mediated by the inhibition of the mTOR, which may serve as a promising agent for the treatment of CCA.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>24527093</pmid><doi>10.3892/ol.2014.1799</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1792-1074 |
| ispartof | Oncology letters, 2014-03, Vol.7 (3), p.854-860 |
| issn | 1792-1074 1792-1082 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3919862 |
| source | Spandidos Publications Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Apoptosis Cancer therapies Cell cycle Cell growth Cholangiocarcinoma Health aspects Kinases mTOR inhibitor Oncology Phosphorylation Phosphotransferases Proteins RAD001 Studies |
| title | Role of mTOR inhibitor in cholangiocarcinoma cell progression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T02%3A47%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Role%20of%20mTOR%20inhibitor%20in%20cholangiocarcinoma%20cell%20progression&rft.jtitle=Oncology%20letters&rft.au=MOOLTHIYA,%20PENPAK&rft.date=2014-03-01&rft.volume=7&rft.issue=3&rft.spage=854&rft.epage=860&rft.pages=854-860&rft.issn=1792-1074&rft.eissn=1792-1082&rft_id=info:doi/10.3892/ol.2014.1799&rft_dat=%3Cgale_pubme%3EA426827950%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1932638775&rft_id=info:pmid/24527093&rft_galeid=A426827950&rfr_iscdi=true |