Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo.
Identifieur interne : 000157 ( PubMed/Corpus ); précédent : 000156; suivant : 000158Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo.
Auteurs : Xiangxiang Hu ; Si Shi ; Huan Wang ; Xiaochen Yu ; Qian Wang ; Shanshan Jiang ; Dianwen Ju ; Li Ye ; Meiqing FengSource :
- Scientific reports [ 2045-2322 ] ; 2017.
English descriptors
- KwdEn :
- Adenocarcinoma of Lung (genetics), Adenocarcinoma of Lung (metabolism), Adenocarcinoma of Lung (pathology), Afatinib (pharmacology), Animals, Apoptosis (drug effects), Apoptosis (genetics), Autophagy (drug effects), Autophagy (genetics), Caspase 3 (metabolism), Cell Line, Tumor, Disease Models, Animal, ErbB Receptors (antagonists & inhibitors), ErbB Receptors (genetics), Humans, Mice, Protein Kinase Inhibitors (pharmacology), Proto-Oncogene Proteins c-akt (metabolism), Reactive Oxygen Species (metabolism), Signal Transduction (drug effects), TOR Serine-Threonine Kinases (metabolism), Xenograft Model Antitumor Assays.
- MESH :
- chemical , antagonists & inhibitors : ErbB Receptors.
- chemical , genetics : ErbB Receptors.
- chemical , metabolism : Caspase 3, Proto-Oncogene Proteins c-akt, Reactive Oxygen Species, TOR Serine-Threonine Kinases.
- chemical , pharmacology : Afatinib, Protein Kinase Inhibitors.
- drug effects : Apoptosis, Autophagy, Signal Transduction.
- genetics : Adenocarcinoma of Lung, Apoptosis, Autophagy.
- metabolism : Adenocarcinoma of Lung.
- pathology : Adenocarcinoma of Lung.
- Animals, Cell Line, Tumor, Disease Models, Animal, Humans, Mice, Xenograft Model Antitumor Assays.
Abstract
Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. Then we confirmed afatinib-induced autophagy in H1975 and H1650 cells. Importantly, autophagy inhibition using chloroquine (CQ) and 3-MA enhanced the cytotoxicity of afatinib, elucidating the cytoprotective role of autophagy in lung adenocarcinoma therapy with afatinib. Further study suggested that Akt/mTOR and Erk signaling pathways were involved in afatinib-induced autophagy, and reactive oxygen species (ROS) acted as an intracellular transducer regulating both autophagy and apoptosis in afatinib-treated H1975 and H1650 cells. Moreover, the in vivo experiment in xenograft model using H1975 cell line confirmed the enhanced anti-lung adenocarcinoma efficacy of afatinib when combined with autophagy inhibitor CQ. Thus, blocking autophagy may be a promising strategy to overcome resistance and increase sensitivity to afatinib in lung adenocarcinoma harboring activating EGFR mutations.
DOI: 10.1038/s41598-017-04258-8
PubMed: 28676644
Links to Exploration step
pubmed:28676644Le document en format XML
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<term>Afatinib (pharmacology)</term>
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<term>Xenograft Model Antitumor Assays</term>
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<front><div type="abstract" xml:lang="en">Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. Then we confirmed afatinib-induced autophagy in H1975 and H1650 cells. Importantly, autophagy inhibition using chloroquine (CQ) and 3-MA enhanced the cytotoxicity of afatinib, elucidating the cytoprotective role of autophagy in lung adenocarcinoma therapy with afatinib. Further study suggested that Akt/mTOR and Erk signaling pathways were involved in afatinib-induced autophagy, and reactive oxygen species (ROS) acted as an intracellular transducer regulating both autophagy and apoptosis in afatinib-treated H1975 and H1650 cells. Moreover, the in vivo experiment in xenograft model using H1975 cell line confirmed the enhanced anti-lung adenocarcinoma efficacy of afatinib when combined with autophagy inhibitor CQ. Thus, blocking autophagy may be a promising strategy to overcome resistance and increase sensitivity to afatinib in lung adenocarcinoma harboring activating EGFR mutations.</div>
</front>
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<Abstract><AbstractText>Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. Then we confirmed afatinib-induced autophagy in H1975 and H1650 cells. Importantly, autophagy inhibition using chloroquine (CQ) and 3-MA enhanced the cytotoxicity of afatinib, elucidating the cytoprotective role of autophagy in lung adenocarcinoma therapy with afatinib. Further study suggested that Akt/mTOR and Erk signaling pathways were involved in afatinib-induced autophagy, and reactive oxygen species (ROS) acted as an intracellular transducer regulating both autophagy and apoptosis in afatinib-treated H1975 and H1650 cells. Moreover, the in vivo experiment in xenograft model using H1975 cell line confirmed the enhanced anti-lung adenocarcinoma efficacy of afatinib when combined with autophagy inhibitor CQ. Thus, blocking autophagy may be a promising strategy to overcome resistance and increase sensitivity to afatinib in lung adenocarcinoma harboring activating EGFR mutations.</AbstractText>
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<ReferenceList><Reference><Citation>Cancer Sci. 2016 Jan;107(1):45-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26545934</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Autophagy. 2007 Jan-Feb;3(1):28-31</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16969128</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Cell Biochem. 2013 Dec;114(12):2643-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23794518</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Manag Res. 2012;4:357-65</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23091399</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Pharmacol Exp Ther. 2012 Nov;343 (2):342-50</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22888144</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2015 Jun 12;10(6):e0129853</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26065685</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>FEBS J. 2010 Jan;277(1):2-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19843174</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Future Oncol. 2015 Sep;11(18):2525-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26314834</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2016 Oct 20;167(3):606-609</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27768885</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell. 2011 Nov 11;147(4):728-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22078875</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Cancer Ther. 2011 Sep;10(9):1533-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21878654</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drugs. 2014 Feb;74(2):207-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24435321</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2013 Aug 28;8(8):e72478</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24015249</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Feb 28;6(6):3861-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25738356</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cancer Sci. 2015 Sep;106(9):1202-11</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26094656</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>PLoS One. 2013 Nov 25;8(11):e81408</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24282590</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Autophagy. 2012 Dec;8(12 ):1724-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22948227</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Death Dis. 2013 Oct 10;4:e840</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24113174</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Tumour Biol. 2016 Jul;37(7):9249-54</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26768746</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Autophagy. 2009 Jan;5(1):3-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19115480</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Am J Transl Res. 2015 Nov 15;7(11):2519-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26807196</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Lung Cancer. 2013 Aug;81(2):155-61</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23664448</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Breast Cancer Res Treat. 2013 Jan;137(2):397-406</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23242584</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Clin Transl Oncol. 2015 Mar;17(3):209-14</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25214146</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Tumour Biol. 2016 Sep;37(9):12597-12607</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27402308</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cell Death Differ. 2015 Mar;22(3):377-88</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25257172</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Appl Microbiol Biotechnol. 2016 Nov;100(21):9145-9161</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27251546</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Science. 2011 Jun 17;332(6036):1429-33</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21617040</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Cells. 2016 May 13;5(2):null</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27187479</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Crit Rev Oncol Hematol. 2016 Apr;100:107-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26852079</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>World J Gastroenterol. 2012 Dec 7;18(45):6537-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23236226</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Cancer Res Clin Oncol. 2015 Mar;141(3):431-41</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25245053</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Mol Med Rep. 2015 Jan;11(1):625-32</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25339370</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Int J Oncol. 2016 Jan;48(1):45-54</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26718641</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Semin Cell Dev Biol. 2014 Dec;36:121-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25158238</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Tumour Biol. 2016 Jul;37(7):9625-33</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26797786</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Curr Cancer Drug Targets. 2013 Sep;13(7):724-34</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23941517</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncogene. 2008 Aug 7;27(34):4702-11</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18408761</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Mar 20;6(8):5832-45</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25714021</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Oncotarget. 2015 Feb 10;6(4):2164-79</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25537503</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>J Clin Invest. 2007 Feb;117(2):326-36</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17235397</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Phytomedicine. 2016 Mar 15;23(3):243-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">26969378</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nature. 2013 Oct 10;502(7470):194-200</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24089209</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Nat Rev Mol Cell Biol. 2007 Sep;8(9):741-52</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17717517</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>BMC Med. 2012 Mar 21;10 :28</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22436374</ArticleId>
</ArticleIdList>
</Reference>
<Reference><Citation>Drugs. 2013 Sep;73(13):1503-15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23982599</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
</record>
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