Oncolytic newcastle disease virus triggers cell death of lung cancer spheroids and is enhanced by pharmacological inhibition of autophagy.
Identifieur interne : 000E78 ( Main/Exploration ); précédent : 000E77; suivant : 000E79Oncolytic newcastle disease virus triggers cell death of lung cancer spheroids and is enhanced by pharmacological inhibition of autophagy.
Auteurs : Lulu Hu [République populaire de Chine] ; Sulan Sun [République populaire de Chine] ; Tianpeng Wang [République populaire de Chine] ; Yingchun Li [République populaire de Chine] ; Ke Jiang [République populaire de Chine] ; Guibin Lin [République populaire de Chine] ; Yan Ma [République populaire de Chine] ; Martin P. Barr [Irlande (pays)] ; Fei Song [République populaire de Chine] ; Guirong Zhang [République populaire de Chine] ; Songshu Meng [République populaire de Chine]Source :
- American journal of cancer research [ 2156-6976 ] ; 2015.
Abstract
Lung cancer stem cells (CSCs) have recently been isolated from lung cancer patient samples and have been reported to be responsible for tumor initiation, treatment resistance and tumor recurrence. We have previously shown that oncolytic Newcastle disease virus (NDV), strain FMW (NDV/FMW) induces apoptosis in drug-resistant lung cancer cells. However, how NDV exerts its oncolytic effect on lung CSCs remains to be investigated. Here we show that NDV/FMW replicates in, and lyses CSC-enriched lung cancer spheroids and inhibits the 3D growth potential of lung cancer spheroid and agar colonies. We demonstrate that NDV/FMW triggers caspase-dependent apoptosis in lung cancer spheroids as shown by increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage. Notably, NDV/FMW infection results in the degradation of microtubule-associated protein 1 light chain 3 (LC3) II and P62, two hallmarks of autophagy maturation, indicating that NDV/FMW promotes autophagy flux in lung cancer cell spheroids. This was further confirmed by the appearance of an increased number of double-membrane vesicles as detected by transmission electron microscopy. We also show that NDV/FMW promotes autophagy degradation in lung cancer spheroids via inhibition of the AKT/mTOR pathway. In addition, treatment of spheroids with the autophagy inhibitor, chloroquine increases NDV/FMW-induced cytotoxicity. Collectively, our data show that oncolytic NDV/FMW may be a potential strategy in targeting lung CSCs.
PubMed: 26885450
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Oncolytic newcastle disease virus triggers cell death of lung cancer spheroids and is enhanced by pharmacological inhibition of autophagy.</title><author><name sortKey="Hu, Lulu" sort="Hu, Lulu" uniqKey="Hu L" first="Lulu" last="Hu">Lulu Hu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Sulan" sort="Sun, Sulan" uniqKey="Sun S" first="Sulan" last="Sun">Sulan Sun</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Tianpeng" sort="Wang, Tianpeng" uniqKey="Wang T" first="Tianpeng" last="Wang">Tianpeng Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Image, Liaoning Cancer Hospital 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Image, Liaoning Cancer Hospital 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yingchun" sort="Li, Yingchun" uniqKey="Li Y" first="Yingchun" last="Li">Yingchun Li</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Guibin" sort="Lin, Guibin" uniqKey="Lin G" first="Guibin" last="Lin">Guibin Lin</name><affiliation wicri:level="1"><nlm:affiliation>College of Bioscience and Biotechnology, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Bioscience and Biotechnology, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009</wicri:regionArea><wicri:noRegion>Yangzhou 225009</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name><affiliation wicri:level="1"><nlm:affiliation>School of Veterinary Medicine, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, Jiangsu, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Veterinary Medicine, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Barr, Martin P" sort="Barr, Martin P" uniqKey="Barr M" first="Martin P" last="Barr">Martin P. Barr</name><affiliation wicri:level="1"><nlm:affiliation>Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin</wicri:regionArea><wicri:noRegion>Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Song, Fei" sort="Song, Fei" uniqKey="Song F" first="Fei" last="Song">Fei Song</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26885450</idno><idno type="pmid">26885450</idno><idno type="wicri:Area/PubMed/Corpus">000218</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000218</idno><idno type="wicri:Area/PubMed/Curation">000218</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000218</idno><idno type="wicri:Area/PubMed/Checkpoint">000230</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" 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Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Sun, Sulan" sort="Sun, Sulan" uniqKey="Sun S" first="Sulan" last="Sun">Sulan Sun</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Tianpeng" sort="Wang, Tianpeng" uniqKey="Wang T" first="Tianpeng" last="Wang">Tianpeng Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Image, Liaoning Cancer Hospital 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Medical Image, Liaoning Cancer Hospital 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Li, Yingchun" sort="Li, Yingchun" uniqKey="Li Y" first="Yingchun" last="Li">Yingchun Li</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Guibin" sort="Lin, Guibin" uniqKey="Lin G" first="Guibin" last="Lin">Guibin Lin</name><affiliation wicri:level="1"><nlm:affiliation>College of Bioscience and Biotechnology, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>College of Bioscience and Biotechnology, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009</wicri:regionArea><wicri:noRegion>Yangzhou 225009</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name><affiliation wicri:level="1"><nlm:affiliation>School of Veterinary Medicine, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, Jiangsu, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Veterinary Medicine, Yangzhou University 48 East, Wenhui Road, Yangzhou 225009, Jiangsu</wicri:regionArea><wicri:noRegion>Jiangsu</wicri:noRegion></affiliation></author><author><name sortKey="Barr, Martin P" sort="Barr, Martin P" uniqKey="Barr M" first="Martin P" last="Barr">Martin P. Barr</name><affiliation wicri:level="1"><nlm:affiliation>Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin, Ireland.</nlm:affiliation><country xml:lang="fr">Irlande (pays)</country><wicri:regionArea>Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin</wicri:regionArea><wicri:noRegion>Trinity Centre for Health Sciences St. James's Hospital & Trinity College Dublin Dublin</wicri:noRegion></affiliation></author><author><name sortKey="Song, Fei" sort="Song, Fei" uniqKey="Song F" first="Fei" last="Song">Fei Song</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Biotherapy Research Center, Liaoning Cancer Hospital & Institute 44 Xiaoheyan Road, Shenyang 110042</wicri:regionArea><wicri:noRegion>Shenyang 110042</wicri:noRegion></affiliation></author><author><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Neurosurgery, Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University Dalian 116044</wicri:regionArea><wicri:noRegion>Dalian Medical University Dalian 116044</wicri:noRegion></affiliation></author></analytic><series><title level="j">American journal of cancer research</title><idno type="ISSN">2156-6976</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lung cancer stem cells (CSCs) have recently been isolated from lung cancer patient samples and have been reported to be responsible for tumor initiation, treatment resistance and tumor recurrence. We have previously shown that oncolytic Newcastle disease virus (NDV), strain FMW (NDV/FMW) induces apoptosis in drug-resistant lung cancer cells. However, how NDV exerts its oncolytic effect on lung CSCs remains to be investigated. Here we show that NDV/FMW replicates in, and lyses CSC-enriched lung cancer spheroids and inhibits the 3D growth potential of lung cancer spheroid and agar colonies. We demonstrate that NDV/FMW triggers caspase-dependent apoptosis in lung cancer spheroids as shown by increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage. Notably, NDV/FMW infection results in the degradation of microtubule-associated protein 1 light chain 3 (LC3) II and P62, two hallmarks of autophagy maturation, indicating that NDV/FMW promotes autophagy flux in lung cancer cell spheroids. This was further confirmed by the appearance of an increased number of double-membrane vesicles as detected by transmission electron microscopy. We also show that NDV/FMW promotes autophagy degradation in lung cancer spheroids via inhibition of the AKT/mTOR pathway. In addition, treatment of spheroids with the autophagy inhibitor, chloroquine increases NDV/FMW-induced cytotoxicity. Collectively, our data show that oncolytic NDV/FMW may be a potential strategy in targeting lung CSCs. </div></front></TEI><affiliations><list><country><li>Irlande (pays)</li><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Hu, Lulu" sort="Hu, Lulu" uniqKey="Hu L" first="Lulu" last="Hu">Lulu Hu</name></noRegion><name sortKey="Jiang, Ke" sort="Jiang, Ke" uniqKey="Jiang K" first="Ke" last="Jiang">Ke Jiang</name><name sortKey="Li, Yingchun" sort="Li, Yingchun" uniqKey="Li Y" first="Yingchun" last="Li">Yingchun Li</name><name sortKey="Lin, Guibin" sort="Lin, Guibin" uniqKey="Lin G" first="Guibin" last="Lin">Guibin Lin</name><name sortKey="Ma, Yan" sort="Ma, Yan" uniqKey="Ma Y" first="Yan" last="Ma">Yan Ma</name><name sortKey="Meng, Songshu" sort="Meng, Songshu" uniqKey="Meng S" first="Songshu" last="Meng">Songshu Meng</name><name sortKey="Song, Fei" sort="Song, Fei" uniqKey="Song F" first="Fei" last="Song">Fei Song</name><name sortKey="Sun, Sulan" sort="Sun, Sulan" uniqKey="Sun S" first="Sulan" last="Sun">Sulan Sun</name><name sortKey="Wang, Tianpeng" sort="Wang, Tianpeng" uniqKey="Wang T" first="Tianpeng" last="Wang">Tianpeng Wang</name><name sortKey="Zhang, Guirong" sort="Zhang, Guirong" uniqKey="Zhang G" first="Guirong" last="Zhang">Guirong Zhang</name></country><country name="Irlande (pays)"><noRegion><name sortKey="Barr, Martin P" sort="Barr, Martin P" uniqKey="Barr M" first="Martin P" last="Barr">Martin P. 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