EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC
Identifieur interne : 000867 ( Main/Exploration ); précédent : 000866; suivant : 000868EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC
Auteurs : Jiao Meng [République populaire de Chine] ; Cuicui Chang [République populaire de Chine] ; Yuhua Chen [République populaire de Chine] ; Fangfang Bi [République populaire de Chine] ; Chen Ji [République populaire de Chine] ; Wei Liu [République populaire de Chine]Source :
- OncoTargets and therapy [ 1178-6930 ] ; 2019.
Abstract
Several EGFR-tyrosine kinase inhibitors (TKIs), such as gefitinib (Gef), have been used as effective clinical therapies for patients with non-small cell lung cancer (NSCLC). However, due to acquired resistance, the efficacy of Gef treatment is severely blocked. Our preliminary study found that epigallocatechin gallate (EGCG) in combination with Gef could work synergistically to increase the sensitivity to Gef in NSCLC, but the mechanisms responsible for this have not been completely defined.
In our present study, we devoted to investigate the synergistic effects of combined EGCG and Gef treatment and the importance of autophagy and ERK signaling pathway in overcoming acquired drug resistance to Gef in NSCLC.
We evaluated the synergistic effects of combined EGCG and Gef treatment through in vitro cell proliferation/viability assays and in vivo xenograft studies, respectively. Autophagic flux was assessed by GFP-microtubule-associated protein 1 light chain 3 (LC3) plasmid transfection and western blot detection of autophagy-related proteins. Besides, the role of ERK on acquired resistance was validated with a ERK inhibitor.
We discovered that EGCG can synergize with Gef to inhibit the proliferation of Gef-resistant NSCLC cells and suppress tumor growth in a xenograft mouse model. The underlying mechanisms of synergism were investigated, and the results showed that co-treatment with Gef and EGCG could inhibit Gef-induced autophagy and ERK phosphorylation. Consistently, the expression of LC3-II/I and ATG5 were inhibited, whereas the expression of p62 was enhanced in EGCG and Gef combination treatment groups. Further, inhibition of autophagy in Gef-resistant A549 cells could augment cell death.
In conclusion, EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.
Url:
DOI: 10.2147/OTT.S209441
PubMed: 31440060
PubMed Central: 6668247
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000737
- to stream Pmc, to step Curation: 000737
- to stream Pmc, to step Checkpoint: 000807
- to stream Ncbi, to step Merge: 000954
- to stream Ncbi, to step Curation: 000954
- to stream Ncbi, to step Checkpoint: 000954
- to stream Main, to step Merge: 000867
- to stream Main, to step Curation: 000867
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC</title><author><name sortKey="Meng, Jiao" sort="Meng, Jiao" uniqKey="Meng J" first="Jiao" last="Meng">Jiao Meng</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Cuicui" sort="Chang, Cuicui" uniqKey="Chang C" first="Cuicui" last="Chang">Cuicui Chang</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuhua" sort="Chen, Yuhua" uniqKey="Chen Y" first="Yuhua" last="Chen">Yuhua Chen</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bi, Fangfang" sort="Bi, Fangfang" uniqKey="Bi F" first="Fangfang" last="Bi">Fangfang Bi</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Chen" sort="Ji, Chen" uniqKey="Ji C" first="Chen" last="Ji">Chen Ji</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31440060</idno><idno type="pmc">6668247</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668247</idno><idno type="RBID">PMC:6668247</idno><idno type="doi">10.2147/OTT.S209441</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000737</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000737</idno><idno type="wicri:Area/Pmc/Curation">000737</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000737</idno><idno type="wicri:Area/Pmc/Checkpoint">000807</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000807</idno><idno type="wicri:Area/Ncbi/Merge">000954</idno><idno type="wicri:Area/Ncbi/Curation">000954</idno><idno type="wicri:Area/Ncbi/Checkpoint">000954</idno><idno type="wicri:Area/Main/Merge">000867</idno><idno type="wicri:Area/Main/Curation">000867</idno><idno type="wicri:Area/Main/Exploration">000867</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC</title><author><name sortKey="Meng, Jiao" sort="Meng, Jiao" uniqKey="Meng J" first="Jiao" last="Meng">Jiao Meng</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Cuicui" sort="Chang, Cuicui" uniqKey="Chang C" first="Cuicui" last="Chang">Cuicui Chang</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yuhua" sort="Chen, Yuhua" uniqKey="Chen Y" first="Yuhua" last="Chen">Yuhua Chen</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bi, Fangfang" sort="Bi, Fangfang" uniqKey="Bi F" first="Fangfang" last="Bi">Fangfang Bi</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ji, Chen" sort="Ji, Chen" uniqKey="Ji C" first="Chen" last="Ji">Chen Ji</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Central Laboratory of Medicine School, Xi’an Peihua University</institution>,<addr-line>Xi’an</addr-line><addr-line>710100</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Medical Science Research Center, Shaanxi Fourth People’s Hospital</institution>,<addr-line>Xi’an</addr-line><addr-line>710143</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">OncoTargets and therapy</title><idno type="eISSN">1178-6930</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S2001"><title>Background</title><p>Several EGFR-tyrosine kinase inhibitors (TKIs), such as gefitinib (Gef), have been used as effective clinical therapies for patients with non-small cell lung cancer (NSCLC). However, due to acquired resistance, the efficacy of Gef treatment is severely blocked. Our preliminary study found that epigallocatechin gallate (EGCG) in combination with Gef could work synergistically to increase the sensitivity to Gef in NSCLC, but the mechanisms responsible for this have not been completely defined.</p></sec><sec id="S2002"><title>Purpose</title><p>In our present study, we devoted to investigate the synergistic effects of combined EGCG and Gef treatment and the importance of autophagy and ERK signaling pathway in overcoming acquired drug resistance to Gef in NSCLC.</p></sec><sec id="S2003"><title>Methods</title><p>We evaluated the synergistic effects of combined EGCG and Gef treatment through in vitro cell proliferation/viability assays and in vivo xenograft studies, respectively. Autophagic flux was assessed by GFP-microtubule-associated protein 1 light chain 3 (LC3) plasmid transfection and western blot detection of autophagy-related proteins. Besides, the role of ERK on acquired resistance was validated with a ERK inhibitor.</p></sec><sec id="S2004"><title>Results</title><p>We discovered that EGCG can synergize with Gef to inhibit the proliferation of Gef-resistant NSCLC cells and suppress tumor growth in a xenograft mouse model. The underlying mechanisms of synergism were investigated, and the results showed that co-treatment with Gef and EGCG could inhibit Gef-induced autophagy and ERK phosphorylation. Consistently, the expression of LC3-II/I and ATG5 were inhibited, whereas the expression of p62 was enhanced in EGCG and Gef combination treatment groups. Further, inhibition of autophagy in Gef-resistant A549 cells could augment cell death.</p></sec><sec id="S2005"><title>Conclusion</title><p>In conclusion, EGCG overcomes Gef resistance by inhibiting autophagy and augmenting cell death through targeting ERK pathway in NSCLC. Gef and EGCG combination therapy may be an effective strategy to overcome acquired resistance in NSCLC.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Meng, Jiao" sort="Meng, Jiao" uniqKey="Meng J" first="Jiao" last="Meng">Jiao Meng</name></noRegion><name sortKey="Bi, Fangfang" sort="Bi, Fangfang" uniqKey="Bi F" first="Fangfang" last="Bi">Fangfang Bi</name><name sortKey="Bi, Fangfang" sort="Bi, Fangfang" uniqKey="Bi F" first="Fangfang" last="Bi">Fangfang Bi</name><name sortKey="Chang, Cuicui" sort="Chang, Cuicui" uniqKey="Chang C" first="Cuicui" last="Chang">Cuicui Chang</name><name sortKey="Chen, Yuhua" sort="Chen, Yuhua" uniqKey="Chen Y" first="Yuhua" last="Chen">Yuhua Chen</name><name sortKey="Chen, Yuhua" sort="Chen, Yuhua" uniqKey="Chen Y" first="Yuhua" last="Chen">Yuhua Chen</name><name sortKey="Ji, Chen" sort="Ji, Chen" uniqKey="Ji C" first="Chen" last="Ji">Chen Ji</name><name sortKey="Liu, Wei" sort="Liu, Wei" uniqKey="Liu W" first="Wei" last="Liu">Wei Liu</name><name sortKey="Meng, Jiao" sort="Meng, Jiao" uniqKey="Meng J" first="Jiao" last="Meng">Jiao Meng</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000867 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000867 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:6668247
|texte= EGCG overcomes gefitinib resistance by inhibiting autophagy and augmenting cell death through targeting ERK phosphorylation in NSCLC
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:31440060" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |