Inhibition of autophagy enhances heat-induced apoptosis in human non-small cell lung cancer cells through ER stress pathways.
Identifieur interne : 000D67 ( Main/Exploration ); précédent : 000D66; suivant : 000D68Inhibition of autophagy enhances heat-induced apoptosis in human non-small cell lung cancer cells through ER stress pathways.
Auteurs : Wen-Yue Xie [République populaire de Chine] ; Xiang-Dong Zhou [République populaire de Chine] ; Juan Yang [République populaire de Chine] ; Ling-Xiu Chen [République populaire de Chine] ; Dan-Hua Ran [République populaire de Chine]Source :
- Archives of biochemistry and biophysics [ 1096-0384 ] ; 2016.
Descripteurs français
- KwdFr :
- Adénine (), Adénine (analogues et dérivés), Animaux, Apoptose (), Autophagie (), Bécline-1 (), Carcinome pulmonaire non à petites cellules (traitement médicamenteux), Cellules A549, Chloroquine (), Cytométrie en flux, Humains, Hyperthermie provoquée, Immunohistochimie, Lignée cellulaire tumorale, Microscopie électronique à transmission, Mâle, Méthode TUNEL, Petit ARN interférent (), Phosphorylation, Réticulum endoplasmique (métabolisme), Souris, Souris de lignée BALB C, Stress du réticulum endoplasmique, Température élevée, Tumeurs du poumon (métabolisme).
- MESH :
- analogues et dérivés : Adénine.
- métabolisme : Réticulum endoplasmique, Tumeurs du poumon.
- traitement médicamenteux : Carcinome pulmonaire non à petites cellules.
- Adénine, Animaux, Apoptose, Autophagie, Bécline-1, Cellules A549, Chloroquine, Cytométrie en flux, Humains, Hyperthermie provoquée, Immunohistochimie, Lignée cellulaire tumorale, Microscopie électronique à transmission, Mâle, Méthode TUNEL, Petit ARN interférent, Phosphorylation, Souris, Souris de lignée BALB C, Stress du réticulum endoplasmique, Température élevée.
English descriptors
- KwdEn :
- A549 Cells, Adenine (analogs & derivatives), Adenine (chemistry), Animals, Apoptosis (drug effects), Autophagy (drug effects), Beclin-1 (chemistry), Carcinoma, Non-Small-Cell Lung (drug therapy), Cell Line, Tumor, Chloroquine (chemistry), Endoplasmic Reticulum (metabolism), Endoplasmic Reticulum Stress, Flow Cytometry, Hot Temperature, Humans, Hyperthermia, Induced, Immunohistochemistry, In Situ Nick-End Labeling, Lung Neoplasms (metabolism), Male, Mice, Mice, Inbred BALB C, Microscopy, Electron, Transmission, Phosphorylation, RNA, Small Interfering (chemistry).
- MESH :
- chemical , analogs & derivatives : Adenine.
- chemical , chemistry : Adenine, Beclin-1, Chloroquine, RNA, Small Interfering.
- drug effects : Apoptosis, Autophagy.
- drug therapy : Carcinoma, Non-Small-Cell Lung.
- metabolism : Endoplasmic Reticulum, Lung Neoplasms.
- A549 Cells, Animals, Cell Line, Tumor, Endoplasmic Reticulum Stress, Flow Cytometry, Hot Temperature, Humans, Hyperthermia, Induced, Immunohistochemistry, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred BALB C, Microscopy, Electron, Transmission, Phosphorylation.
Abstract
The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent). Further, heat treatment led to the increased phosphorylation of AMPK and the decreased phosphorylation of mTOR in vitro and in vivo. Knockdown of GRP78 inhibited the AMPK-mTOR pathway, and the AMPK inhibitor compound C decreased heat-induced autophagy, suggesting that activation of ER stress was involved in autophagy induction and promotion of the AMPK-mTOR pathway. In conclusion, our data suggested that the heat treatment of lung cancer cells triggered protective autophagy, as mediated by ER stress. Thus, inhibition of autophagy can be a promising strategy to enhance hyperthermia in the treatment of lung cancer patients.
DOI: 10.1016/j.abb.2016.08.016
PubMed: 27565443
Affiliations:
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Electronic address: xiewy112@sina.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oncology, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Xiang Dong" sort="Zhou, Xiang Dong" uniqKey="Zhou X" first="Xiang-Dong" last="Zhou">Xiang-Dong Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China; Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China; Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou</wicri:regionArea><wicri:noRegion>Haikou</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Juan" sort="Yang, Juan" uniqKey="Yang J" first="Juan" last="Yang">Juan Yang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Ling Xiu" sort="Chen, Ling Xiu" uniqKey="Chen L" first="Ling-Xiu" last="Chen">Ling-Xiu Chen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Ran, Dan Hua" sort="Ran, Dan Hua" uniqKey="Ran D" first="Dan-Hua" last="Ran">Dan-Hua Ran</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27565443</idno><idno type="pmid">27565443</idno><idno type="doi">10.1016/j.abb.2016.08.016</idno><idno type="wicri:Area/PubMed/Corpus">000196</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000196</idno><idno type="wicri:Area/PubMed/Curation">000196</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000196</idno><idno type="wicri:Area/PubMed/Checkpoint">000202</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000202</idno><idno type="wicri:Area/Ncbi/Merge">000354</idno><idno type="wicri:Area/Ncbi/Curation">000354</idno><idno type="wicri:Area/Ncbi/Checkpoint">000354</idno><idno type="wicri:Area/Main/Merge">000D68</idno><idno type="wicri:Area/Main/Curation">000D67</idno><idno type="wicri:Area/Main/Exploration">000D67</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Inhibition of autophagy enhances heat-induced apoptosis in human non-small cell lung cancer cells through ER stress pathways.</title><author><name sortKey="Xie, Wen Yue" sort="Xie, Wen Yue" uniqKey="Xie W" first="Wen-Yue" last="Xie">Wen-Yue Xie</name><affiliation wicri:level="1"><nlm:affiliation>Department of Oncology, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China. Electronic address: xiewy112@sina.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Oncology, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Zhou, Xiang Dong" sort="Zhou, Xiang Dong" uniqKey="Zhou X" first="Xiang-Dong" last="Zhou">Xiang-Dong Zhou</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China; Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China; Division of Respiratory Medicine, Affiliated Hospital of Hainan Medical University, Haikou</wicri:regionArea><wicri:noRegion>Haikou</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Juan" sort="Yang, Juan" uniqKey="Yang J" first="Juan" last="Yang">Juan Yang</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing Academy of Traditional Chinese Medicine, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Ling Xiu" sort="Chen, Ling Xiu" uniqKey="Chen L" first="Ling-Xiu" last="Chen">Ling-Xiu Chen</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author><author><name sortKey="Ran, Dan Hua" sort="Ran, Dan Hua" uniqKey="Ran D" first="Dan-Hua" last="Ran">Dan-Hua Ran</name><affiliation wicri:level="1"><nlm:affiliation>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No.74, Linjiang Road, Yuzhong District, Chongqing 400010</wicri:regionArea><wicri:noRegion>Chongqing 400010</wicri:noRegion></affiliation></author></analytic><series><title level="j">Archives of biochemistry and biophysics</title><idno type="eISSN">1096-0384</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>A549 Cells</term><term>Adenine (analogs & derivatives)</term><term>Adenine (chemistry)</term><term>Animals</term><term>Apoptosis (drug effects)</term><term>Autophagy (drug effects)</term><term>Beclin-1 (chemistry)</term><term>Carcinoma, Non-Small-Cell Lung (drug therapy)</term><term>Cell Line, Tumor</term><term>Chloroquine (chemistry)</term><term>Endoplasmic Reticulum (metabolism)</term><term>Endoplasmic Reticulum Stress</term><term>Flow Cytometry</term><term>Hot Temperature</term><term>Humans</term><term>Hyperthermia, Induced</term><term>Immunohistochemistry</term><term>In Situ Nick-End Labeling</term><term>Lung Neoplasms (metabolism)</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Microscopy, Electron, Transmission</term><term>Phosphorylation</term><term>RNA, Small Interfering (chemistry)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adénine ()</term><term>Adénine (analogues et dérivés)</term><term>Animaux</term><term>Apoptose ()</term><term>Autophagie ()</term><term>Bécline-1 ()</term><term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term><term>Cellules A549</term><term>Chloroquine ()</term><term>Cytométrie en flux</term><term>Humains</term><term>Hyperthermie provoquée</term><term>Immunohistochimie</term><term>Lignée cellulaire tumorale</term><term>Microscopie électronique à transmission</term><term>Mâle</term><term>Méthode TUNEL</term><term>Petit ARN interférent ()</term><term>Phosphorylation</term><term>Réticulum endoplasmique (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Stress du réticulum endoplasmique</term><term>Température élevée</term><term>Tumeurs du poumon (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Adenine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Adenine</term><term>Beclin-1</term><term>Chloroquine</term><term>RNA, Small Interfering</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Adénine</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Autophagy</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Non-Small-Cell Lung</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Endoplasmic Reticulum</term><term>Lung Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Réticulum endoplasmique</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term></keywords><keywords scheme="MESH" xml:lang="en"><term>A549 Cells</term><term>Animals</term><term>Cell Line, Tumor</term><term>Endoplasmic Reticulum Stress</term><term>Flow Cytometry</term><term>Hot Temperature</term><term>Humans</term><term>Hyperthermia, Induced</term><term>Immunohistochemistry</term><term>In Situ Nick-End Labeling</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Microscopy, Electron, Transmission</term><term>Phosphorylation</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adénine</term><term>Animaux</term><term>Apoptose</term><term>Autophagie</term><term>Bécline-1</term><term>Cellules A549</term><term>Chloroquine</term><term>Cytométrie en flux</term><term>Humains</term><term>Hyperthermie provoquée</term><term>Immunohistochimie</term><term>Lignée cellulaire tumorale</term><term>Microscopie électronique à transmission</term><term>Mâle</term><term>Méthode TUNEL</term><term>Petit ARN interférent</term><term>Phosphorylation</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Stress du réticulum endoplasmique</term><term>Température élevée</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent). Further, heat treatment led to the increased phosphorylation of AMPK and the decreased phosphorylation of mTOR in vitro and in vivo. Knockdown of GRP78 inhibited the AMPK-mTOR pathway, and the AMPK inhibitor compound C decreased heat-induced autophagy, suggesting that activation of ER stress was involved in autophagy induction and promotion of the AMPK-mTOR pathway. In conclusion, our data suggested that the heat treatment of lung cancer cells triggered protective autophagy, as mediated by ER stress. Thus, inhibition of autophagy can be a promising strategy to enhance hyperthermia in the treatment of lung cancer patients.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Xie, Wen Yue" sort="Xie, Wen Yue" uniqKey="Xie W" first="Wen-Yue" last="Xie">Wen-Yue Xie</name></noRegion><name sortKey="Chen, Ling Xiu" sort="Chen, Ling Xiu" uniqKey="Chen L" first="Ling-Xiu" last="Chen">Ling-Xiu Chen</name><name sortKey="Ran, Dan Hua" sort="Ran, Dan Hua" uniqKey="Ran D" first="Dan-Hua" last="Ran">Dan-Hua Ran</name><name sortKey="Yang, Juan" sort="Yang, Juan" uniqKey="Yang J" first="Juan" last="Yang">Juan Yang</name><name sortKey="Zhou, Xiang Dong" sort="Zhou, Xiang Dong" uniqKey="Zhou X" first="Xiang-Dong" last="Zhou">Xiang-Dong Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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