In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC
Objective:To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.Methods:MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549.Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group...
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| Veröffentlicht in: | Asian Pacific journal of tropical medicine 2014-05, Vol.7 (5), p.394-397 |
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| description | Objective:To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.Methods:MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549.Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h.RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.Results:MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells.Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest,which was time-dependent(P<0.05).RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.Conclusions:mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC,which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549.The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study. |
| doi_str_mv | 10.1016/S1995-7645(14)60063-8 |
| format | Article |
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Published by Elsevier B.V. All rights reserved.</rights><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-523eec514ba96bd9ae29d5bb1b7cfd478951b8111074e54a5c80d709c00db0403</citedby><cites>FETCH-LOGICAL-c541t-523eec514ba96bd9ae29d5bb1b7cfd478951b8111074e54a5c80d709c00db0403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/71792X/71792X.jpg</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1995-7645(14)60063-8$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25063068$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiang, Xu-Dong</creatorcontrib><creatorcontrib>Yu, Jing</creatorcontrib><creatorcontrib>Li, Gao-Feng</creatorcontrib><creatorcontrib>Xie, Lin</creatorcontrib><creatorcontrib>Li, Heng</creatorcontrib><title>In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC</title><title>Asian Pacific journal of tropical medicine</title><addtitle>Asian Pacific Journal of Tropical Medicine</addtitle><description>Objective:To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.Methods:MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549.Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h.RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.Results:MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells.Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest,which was time-dependent(P&lt;0.05).RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.Conclusions:mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC,which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549.The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.</description><subject>Adaptor Proteins, Signal Transducing - analysis</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>EGFR</subject><subject>Everolimus</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Lung Neoplasms - metabolism</subject><subject>mTOR</subject><subject>NSCLC</subject><subject>Phosphoproteins - analysis</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>PTEN Phosphohydrolase - analysis</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Signal Transduction - drug effects</subject><subject>Sirolimus - analogs & derivatives</subject><subject>Sirolimus - pharmacology</subject><subject>Targeted</subject><subject>Targeted therapy</subject><subject>therapy</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><issn>1995-7645</issn><issn>2352-4146</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkVtrGzEQRkVpaUyan9Ai6Eta2Fb3y1MpJhcTk0DiPgutJDtKba0j7SZsfn13Yzf0LdXLIDgz8zEHgI8YfcMIi-83WGteScH4MWZfBEKCVuoNmBDKScUwE2_B5AU5AEel3KHhUaK1pO_BAeFDBxJqAi5nCT7ENjewtJ3vYZNgvW7c75hWcLO4uoYlrpJdj9-tbW8fbQ9jgidnp9fV4mIGcyixtDa5AC9vpvPpB_BuadclHO3rIfh1erKYnlfzq7PZ9Oe8cpzhtuKEhuA4ZrXVovbaBqI9r2tcS7f0TCrNca0wxkiywJnlTiEvkXYI-RoxRA_B193cR5uWNq3MXdPlIWcxffZ9__RkAkGYIY4wGeDjHbzNzX0XSms2sbiwXtsUmq4YLASiSkmB_wMlZDi31up1lDMlqMJ6nMp3qMtNKTkszTbHjc29wciMQs2zUDPaMpiZZ6FmXPFpv6KrN8G_dP3VNwA_dkAYbv0QQzbFxTDY8DEH1xrfxFdXfN5Hu23S6n7w_E82RBEVUkr6B181t8U</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Xiang, Xu-Dong</creator><creator>Yu, Jing</creator><creator>Li, Gao-Feng</creator><creator>Xie, Lin</creator><creator>Li, Heng</creator><general>Elsevier B.V</general><general>Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China%Department of Gynecologic 0ncology, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China%Department of Medical 0ncology, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China%Kunming Medical University, Kunming 650118, China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>C1K</scope><scope>F1W</scope><scope>H95</scope><scope>H97</scope><scope>L.G</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20140501</creationdate><title>In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC</title><author>Xiang, Xu-Dong ; Yu, Jing ; Li, Gao-Feng ; Xie, Lin ; Li, Heng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-523eec514ba96bd9ae29d5bb1b7cfd478951b8111074e54a5c80d709c00db0403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Signal Transducing - 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| fulltext | fulltext |
| identifier | ISSN: 1995-7645 |
| ispartof | Asian Pacific journal of tropical medicine, 2014-05, Vol.7 (5), p.394-397 |
| issn | 1995-7645 2352-4146 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adaptor Proteins, Signal Transducing - analysis Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Antineoplastic Agents - pharmacology Apoptosis - drug effects Carcinoma, Non-Small-Cell Lung - metabolism Cell Line, Tumor Cell Proliferation - drug effects EGFR Everolimus Gene Expression Regulation, Neoplastic - drug effects Humans Lung Neoplasms - metabolism mTOR NSCLC Phosphoproteins - analysis Phosphoproteins - genetics Phosphoproteins - metabolism PTEN Phosphohydrolase - analysis PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism Receptor, Epidermal Growth Factor - antagonists & inhibitors Signal Transduction - drug effects Sirolimus - analogs & derivatives Sirolimus - pharmacology Targeted Targeted therapy therapy TOR Serine-Threonine Kinases - metabolism |
| title | In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC |
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