Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress.
Identifieur interne : 000D77 ( Main/Exploration ); précédent : 000D76; suivant : 000D78Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress.
Auteurs : Zhongliang Wang [République populaire de Chine] ; Tingting Du [République populaire de Chine] ; Xiaorong Dong [République populaire de Chine] ; Zhenyu Li [République populaire de Chine] ; Gang Wu [République populaire de Chine] ; Ruiguang Zhang [République populaire de Chine]Source :
- International journal of oncology [ 1791-2423 ] ; 2016.
Descripteurs français
- KwdFr :
- Antinéoplasiques (pharmacologie), Autophagie (), Carcinome pulmonaire non à petites cellules (métabolisme), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Chlorhydrate d'erlotinib (pharmacologie), Chloroquine (pharmacologie), Facteur de transcription CHOP (génétique), Humains, Inhibiteurs de protéines kinases (pharmacologie), Lignée cellulaire tumorale, Petit ARN interférent (pharmacologie), Prolifération cellulaire (), Récepteurs ErbB (antagonistes et inhibiteurs), Résistance aux médicaments antinéoplasiques (), Stress du réticulum endoplasmique (), Survie cellulaire (), Synergie des médicaments, Tumeurs du poumon (métabolisme), Tumeurs du poumon (traitement médicamenteux).
- MESH :
- antagonistes et inhibiteurs : Récepteurs ErbB.
- génétique : Facteur de transcription CHOP.
- métabolisme : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- pharmacologie : Antinéoplasiques, Chlorhydrate d'erlotinib, Chloroquine, Inhibiteurs de protéines kinases, Petit ARN interférent.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules, Tumeurs du poumon.
- Autophagie, Humains, Lignée cellulaire tumorale, Prolifération cellulaire, Résistance aux médicaments antinéoplasiques, Stress du réticulum endoplasmique, Survie cellulaire, Synergie des médicaments.
English descriptors
- KwdEn :
- Antineoplastic Agents (pharmacology), Autophagy (drug effects), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (metabolism), Cell Line, Tumor, Cell Proliferation (drug effects), Cell Survival (drug effects), Chloroquine (pharmacology), Drug Resistance, Neoplasm (drug effects), Drug Synergism, Endoplasmic Reticulum Stress (drug effects), ErbB Receptors (antagonists & inhibitors), Erlotinib Hydrochloride (pharmacology), Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (metabolism), Protein Kinase Inhibitors (pharmacology), RNA, Small Interfering (pharmacology), Transcription Factor CHOP (genetics).
- MESH :
- chemical , antagonists & inhibitors : ErbB Receptors.
- chemical , genetics : Transcription Factor CHOP.
- chemical , pharmacology : Antineoplastic Agents, Chloroquine, Erlotinib Hydrochloride, Protein Kinase Inhibitors, RNA, Small Interfering.
- drug effects : Autophagy, Cell Proliferation, Cell Survival, Drug Resistance, Neoplasm, Endoplasmic Reticulum Stress.
- drug therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- metabolism : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- Cell Line, Tumor, Drug Synergism, Humans.
Abstract
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment for non-small cell lung cancer patients, but acquired resistance limit the efficiency of this treatment. As a homeostatic cellular recycling mechanism, autophagy has been proposed to participate in the EGFR-TKI resistance. However, the role of autophagy in lung cancer treatment and the underlying mechanisms have not been clarified. In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer cells from this co-treatment-induced cell death. Our findings suggest that autophagy inhibition overcomes erlotinib resistance through modulation of ER stress mediated apoptosis.
DOI: 10.3892/ijo.2016.3468
PubMed: 27035631
Affiliations:
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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Du, Tingting" sort="Du, Tingting" uniqKey="Du T" first="Tingting" last="Du">Tingting Du</name><affiliation wicri:level="1"><nlm:affiliation>Department of Endocrinology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Endocrinology, Wuhan Medical and Health Center for Women and Children, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Dong, Xiaorong" sort="Dong, Xiaorong" uniqKey="Dong X" first="Xiaorong" last="Dong">Xiaorong Dong</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Li, Zhenyu" sort="Li, Zhenyu" uniqKey="Li Z" first="Zhenyu" last="Li">Zhenyu Li</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Gang" sort="Wu, Gang" uniqKey="Wu G" first="Gang" last="Wu">Gang Wu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Ruiguang" sort="Zhang, Ruiguang" uniqKey="Zhang R" first="Ruiguang" last="Zhang">Ruiguang Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author></analytic><series><title level="j">International journal of oncology</title><idno type="eISSN">1791-2423</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antineoplastic Agents (pharmacology)</term><term>Autophagy (drug effects)</term><term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term><term>Carcinoma, Non-Small-Cell Lung (metabolism)</term><term>Cell Line, Tumor</term><term>Cell Proliferation (drug effects)</term><term>Cell Survival (drug effects)</term><term>Chloroquine (pharmacology)</term><term>Drug Resistance, Neoplasm (drug effects)</term><term>Drug Synergism</term><term>Endoplasmic Reticulum Stress (drug effects)</term><term>ErbB Receptors (antagonists & inhibitors)</term><term>Erlotinib Hydrochloride (pharmacology)</term><term>Humans</term><term>Lung Neoplasms (drug therapy)</term><term>Lung Neoplasms (metabolism)</term><term>Protein Kinase Inhibitors (pharmacology)</term><term>RNA, Small Interfering (pharmacology)</term><term>Transcription Factor CHOP (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Antinéoplasiques (pharmacologie)</term><term>Autophagie ()</term><term>Carcinome pulmonaire non à petites cellules (métabolisme)</term><term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term><term>Chlorhydrate d'erlotinib (pharmacologie)</term><term>Chloroquine (pharmacologie)</term><term>Facteur de transcription CHOP (génétique)</term><term>Humains</term><term>Inhibiteurs de protéines kinases (pharmacologie)</term><term>Lignée cellulaire tumorale</term><term>Petit ARN interférent (pharmacologie)</term><term>Prolifération cellulaire ()</term><term>Récepteurs ErbB (antagonistes et inhibiteurs)</term><term>Résistance aux médicaments antinéoplasiques ()</term><term>Stress du réticulum endoplasmique ()</term><term>Survie cellulaire ()</term><term>Synergie des médicaments</term><term>Tumeurs du poumon (métabolisme)</term><term>Tumeurs du poumon (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>ErbB Receptors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Transcription Factor CHOP</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antineoplastic Agents</term><term>Chloroquine</term><term>Erlotinib Hydrochloride</term><term>Protein Kinase Inhibitors</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Récepteurs ErbB</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term><term>Cell Proliferation</term><term>Cell Survival</term><term>Drug Resistance, Neoplasm</term><term>Endoplasmic Reticulum Stress</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de transcription CHOP</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antinéoplasiques</term><term>Chlorhydrate d'erlotinib</term><term>Chloroquine</term><term>Inhibiteurs de protéines kinases</term><term>Petit ARN interférent</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Drug Synergism</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Autophagie</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Prolifération cellulaire</term><term>Résistance aux médicaments antinéoplasiques</term><term>Stress du réticulum endoplasmique</term><term>Survie cellulaire</term><term>Synergie des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment for non-small cell lung cancer patients, but acquired resistance limit the efficiency of this treatment. As a homeostatic cellular recycling mechanism, autophagy has been proposed to participate in the EGFR-TKI resistance. However, the role of autophagy in lung cancer treatment and the underlying mechanisms have not been clarified. In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer cells from this co-treatment-induced cell death. Our findings suggest that autophagy inhibition overcomes erlotinib resistance through modulation of ER stress mediated apoptosis. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Wang, Zhongliang" sort="Wang, Zhongliang" uniqKey="Wang Z" first="Zhongliang" last="Wang">Zhongliang Wang</name></noRegion><name sortKey="Dong, Xiaorong" sort="Dong, Xiaorong" uniqKey="Dong X" first="Xiaorong" last="Dong">Xiaorong Dong</name><name sortKey="Du, Tingting" sort="Du, Tingting" uniqKey="Du T" first="Tingting" last="Du">Tingting Du</name><name sortKey="Li, Zhenyu" sort="Li, Zhenyu" uniqKey="Li Z" first="Zhenyu" last="Li">Zhenyu Li</name><name sortKey="Wu, Gang" sort="Wu, Gang" uniqKey="Wu G" first="Gang" last="Wu">Gang Wu</name><name sortKey="Zhang, Ruiguang" sort="Zhang, Ruiguang" uniqKey="Zhang R" first="Ruiguang" last="Zhang">Ruiguang Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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