A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis
Identifieur interne : 000347 ( Pmc/Curation ); précédent : 000346; suivant : 000348A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis
Auteurs : Lihong Chang ; Zizhen Huang ; Shuaixiang Li ; Zhouzhou Yao ; Hongwei Bao ; Zhiyuan Wang ; Xia Li ; Xiaohong Chen ; Jiancong Huang ; Gehua ZhangSource :
- American Journal of Cancer Research [ 2156-6976 ] ; 2019.
Abstract
Activation of the PI3K/mTOR pathways is significantly correlated with a poor prognosis in nasopharyngeal carcinoma (NPC). Inhibition of these pathways was reported to be effective in restoring radiosensitivity. In this study, the activity of the novel ATP-competitive, orally bioavailable mTOR inhibitor AZD8055 was found to inhibit the phosphorylated mTOR and NPC cells proliferation. The IC50 doses in CNE1 and CNE2 cell lines were 60 and 100 nanomolar, respectively. AZD8055 significantly enhanced the inhibitions of cell growth and colony formation induced by irradiation (
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PubMed: 31598395
PubMed Central: 6780664
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis</title><author><name sortKey="Chang, Lihong" sort="Chang, Lihong" uniqKey="Chang L" first="Lihong" last="Chang">Lihong Chang</name></author><author><name sortKey="Huang, Zizhen" sort="Huang, Zizhen" uniqKey="Huang Z" first="Zizhen" last="Huang">Zizhen Huang</name></author><author><name sortKey="Li, Shuaixiang" sort="Li, Shuaixiang" uniqKey="Li S" first="Shuaixiang" last="Li">Shuaixiang Li</name></author><author><name sortKey="Yao, Zhouzhou" sort="Yao, Zhouzhou" uniqKey="Yao Z" first="Zhouzhou" last="Yao">Zhouzhou Yao</name></author><author><name sortKey="Bao, Hongwei" sort="Bao, Hongwei" uniqKey="Bao H" first="Hongwei" last="Bao">Hongwei Bao</name></author><author><name sortKey="Wang, Zhiyuan" sort="Wang, Zhiyuan" uniqKey="Wang Z" first="Zhiyuan" last="Wang">Zhiyuan Wang</name></author><author><name sortKey="Li, Xia" sort="Li, Xia" uniqKey="Li X" first="Xia" last="Li">Xia Li</name></author><author><name sortKey="Chen, Xiaohong" sort="Chen, Xiaohong" uniqKey="Chen X" first="Xiaohong" last="Chen">Xiaohong Chen</name></author><author><name sortKey="Huang, Jiancong" sort="Huang, Jiancong" uniqKey="Huang J" first="Jiancong" last="Huang">Jiancong Huang</name></author><author><name sortKey="Zhang, Gehua" sort="Zhang, Gehua" uniqKey="Zhang G" first="Gehua" last="Zhang">Gehua Zhang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31598395</idno><idno type="pmc">6780664</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780664</idno><idno type="RBID">PMC:6780664</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000347</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000347</idno><idno type="wicri:Area/Pmc/Curation">000347</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000347</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis</title><author><name sortKey="Chang, Lihong" sort="Chang, Lihong" uniqKey="Chang L" first="Lihong" last="Chang">Lihong Chang</name></author><author><name sortKey="Huang, Zizhen" sort="Huang, Zizhen" uniqKey="Huang Z" first="Zizhen" last="Huang">Zizhen Huang</name></author><author><name sortKey="Li, Shuaixiang" sort="Li, Shuaixiang" uniqKey="Li S" first="Shuaixiang" last="Li">Shuaixiang Li</name></author><author><name sortKey="Yao, Zhouzhou" sort="Yao, Zhouzhou" uniqKey="Yao Z" first="Zhouzhou" last="Yao">Zhouzhou Yao</name></author><author><name sortKey="Bao, Hongwei" sort="Bao, Hongwei" uniqKey="Bao H" first="Hongwei" last="Bao">Hongwei Bao</name></author><author><name sortKey="Wang, Zhiyuan" sort="Wang, Zhiyuan" uniqKey="Wang Z" first="Zhiyuan" last="Wang">Zhiyuan Wang</name></author><author><name sortKey="Li, Xia" sort="Li, Xia" uniqKey="Li X" first="Xia" last="Li">Xia Li</name></author><author><name sortKey="Chen, Xiaohong" sort="Chen, Xiaohong" uniqKey="Chen X" first="Xiaohong" last="Chen">Xiaohong Chen</name></author><author><name sortKey="Huang, Jiancong" sort="Huang, Jiancong" uniqKey="Huang J" first="Jiancong" last="Huang">Jiancong Huang</name></author><author><name sortKey="Zhang, Gehua" sort="Zhang, Gehua" uniqKey="Zhang G" first="Gehua" last="Zhang">Gehua Zhang</name></author></analytic><series><title level="j">American Journal of Cancer Research</title><idno type="eISSN">2156-6976</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Activation of the PI3K/mTOR pathways is significantly correlated with a poor prognosis in nasopharyngeal carcinoma (NPC). Inhibition of these pathways was reported to be effective in restoring radiosensitivity. In this study, the activity of the novel ATP-competitive, orally bioavailable mTOR inhibitor AZD8055 was found to inhibit the phosphorylated mTOR and NPC cells proliferation. The IC50 doses in CNE1 and CNE2 cell lines were 60 and 100 nanomolar, respectively. AZD8055 significantly enhanced the inhibitions of cell growth and colony formation induced by irradiation (<italic>P</italic> < 0.05 for all). AZD8055 at the IC50 doses prolonged G2/M arrest (<italic>P</italic> < 0.05) and promoted the apoptosis (<italic>P</italic> < 0.01) induced by irradiation and autophagy in NPC cells. Blocking autophagy weaken the cell growth inhibition and decreased apoptosis induced by AZD8055 combined with irradiation. Treatment with AZD8055 at 5, 10 and 20 mg/kg/d significantly enhanced NPC cell radiosensitivity <italic>in vivo</italic> and significantly induced apoptosis and autophagy in tumor tissues, Neither 5 nor 20 mg/kg/d AZD8055 induced significantly pro-apoptosis bax expressions in mouse livers and kidneys. 5 mg/kg/d produced good radiosensitivity but had little impact on body weight. We concluded that AZD8055 was a promising candidate radiosensitizer for NPC.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Cancer Res</journal-id><journal-id journal-id-type="iso-abbrev">Am J Cancer Res</journal-id><journal-id journal-id-type="publisher-id">ajcr</journal-id><journal-title-group><journal-title>American Journal of Cancer Research</journal-title></journal-title-group><issn pub-type="epub">2156-6976</issn><publisher><publisher-name>e-Century Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31598395</article-id><article-id pub-id-type="pmc">6780664</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>A low dose of AZD8055 enhances radiosensitivity of nasopharyngeal carcinoma cells by activating autophagy and apoptosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Chang</surname><given-names>Lihong</given-names></name><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Zizhen</given-names></name><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Shuaixiang</given-names></name><xref ref-type="author-notes" rid="fn1">*</xref></contrib><contrib contrib-type="author"><name><surname>Yao</surname><given-names>Zhouzhou</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bao</surname><given-names>Hongwei</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Zhiyuan</given-names></name></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>Xia</given-names></name></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xiaohong</given-names></name></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Jiancong</given-names></name></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Gehua</given-names></name></contrib><aff><institution>Department of Otolaryngology-Head & Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University</institution><addr-line>NO. 600 Tianhe Road, Guangzhou 510630, China</addr-line></aff></contrib-group><author-notes><corresp><bold>Address correspondence to:</bold> Gehua Zhang and Jiancong Huang, Department of Otolaryngology-Head & Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. E-mail: <email>zhanggeh@mail.sysu.edu.cn</email> (GHZ); <email>sallot33@hotmail.com</email> (JCH)</corresp><fn id="fn1"><label>*</label><p>Equal contributors.</p></fn></author-notes><pub-date pub-type="collection"><year>2019</year></pub-date><pub-date pub-type="epub"><day>01</day><month>9</month><year>2019</year></pub-date><volume>9</volume><issue>9</issue><fpage>1922</fpage><lpage>1937</lpage><history><date date-type="received"><day>06</day><month>5</month><year>2019</year></date><date date-type="accepted"><day>28</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>AJCR Copyright © 2019</copyright-statement><copyright-year>2019</copyright-year></permissions><abstract><p>Activation of the PI3K/mTOR pathways is significantly correlated with a poor prognosis in nasopharyngeal carcinoma (NPC). Inhibition of these pathways was reported to be effective in restoring radiosensitivity. In this study, the activity of the novel ATP-competitive, orally bioavailable mTOR inhibitor AZD8055 was found to inhibit the phosphorylated mTOR and NPC cells proliferation. The IC50 doses in CNE1 and CNE2 cell lines were 60 and 100 nanomolar, respectively. AZD8055 significantly enhanced the inhibitions of cell growth and colony formation induced by irradiation (<italic>P</italic> < 0.05 for all). AZD8055 at the IC50 doses prolonged G2/M arrest (<italic>P</italic> < 0.05) and promoted the apoptosis (<italic>P</italic> < 0.01) induced by irradiation and autophagy in NPC cells. Blocking autophagy weaken the cell growth inhibition and decreased apoptosis induced by AZD8055 combined with irradiation. Treatment with AZD8055 at 5, 10 and 20 mg/kg/d significantly enhanced NPC cell radiosensitivity <italic>in vivo</italic> and significantly induced apoptosis and autophagy in tumor tissues, Neither 5 nor 20 mg/kg/d AZD8055 induced significantly pro-apoptosis bax expressions in mouse livers and kidneys. 5 mg/kg/d produced good radiosensitivity but had little impact on body weight. We concluded that AZD8055 was a promising candidate radiosensitizer for NPC.</p></abstract><kwd-group><kwd>Nasopharyngeal carcinoma cells cells</kwd><kwd>AZD8055</kwd><kwd>radiosensitivity</kwd><kwd>low dose</kwd><kwd>autophagy</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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