ChloroquineV1, Main, Exploration, bibRecord, 000509

Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer.

Identifieur interne : 000509 ( Main/Exploration ); précédent : 000508; suivant : 000510

Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer.

Source :

Cancer letters [ 1872-7980 ] ; 2019.

RBID : pubmed:30910592

Descripteurs français

English descriptors

KwdEn :
- Acrylamides (pharmacology), Aldehyde Dehydrogenase 1 (biosynthesis), Aniline Compounds (pharmacology), Animals, Antineoplastic Agents (pharmacology), Autophagy (drug effects), Beclin-1 (genetics), Carcinoma, Non-Small-Cell Lung (drug therapy), Carcinoma, Non-Small-Cell Lung (pathology), Cell Line, Tumor, Chloroquine (pharmacology), Drug Resistance, Neoplasm (genetics), ErbB Receptors (genetics), Female, Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (pathology), Mice, Mice, Inbred BALB C, Protein Kinase Inhibitors (pharmacology), RNA Interference, RNA, Small Interfering (genetics), Retinal Dehydrogenase (biosynthesis), SOXB1 Transcription Factors (biosynthesis), Xenograft Model Antitumor Assays.
MESH :
- chemical , biosynthesis : Aldehyde Dehydrogenase 1, Retinal Dehydrogenase, SOXB1 Transcription Factors.
- chemical , genetics : Beclin-1, ErbB Receptors, RNA, Small Interfering.
- chemical , pharmacology : Acrylamides, Aniline Compounds, Antineoplastic Agents, Chloroquine, Protein Kinase Inhibitors.
- drug effects : Autophagy.
- drug therapy : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- genetics : Drug Resistance, Neoplasm.
- pathology : Carcinoma, Non-Small-Cell Lung, Lung Neoplasms.
- Animals, Cell Line, Tumor, Female, Humans, Mice, Mice, Inbred BALB C, RNA Interference, Xenograft Model Antitumor Assays.

Abstract

Osimertinib, a third-generation epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI), shows great efficacy in EGFR-mutant non-small cell lung cancer (NSCLC); however, the resistance is inevitable. Osimertinib induces autophagy in NSCLC cells, but the role of autophagy in osimertinib resistance is not clear. We discovered that enhanced autophagy is associated with osimertinib resistance in vitro and in vivo. Inhibition of autophagy enhanced osimertinib cytotoxicity in both osimertinib-resistant and sensitive cells. Moreover, osimertinib-resistant cells exhibited stem cell-like properties, whereas autophagy inhibition decreased the stemness by downregulating the expression of SOX2 and ALDH1A1. Further, we found that knockdown of Beclin-1 inhibited the stem cell-like properties and restored osimertinib cytotoxicity. Osimertinib combined with chloroquine inhibited tumor growth more effectively than alone in xenograft mice. These results reveal that autophagy plays an adverse role in osimertinib cytotoxicity through inducing stem cell-like properties. Combination therapy of EGFR-TKI and autophagy inhibitor could provide a promising strategy to improve osimertinib cytotoxicity.

DOI: 10.1016/j.canlet.2019.03.027
PubMed: 30910592

Affiliations:

République populaire de Chine

Le document en format XML

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<author><name sortKey="Zhang, Dadong" sort="Zhang, Dadong" uniqKey="Zhang D" first="Dadong" last="Zhang">Dadong Zhang</name>
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<author><name sortKey="Feng, Mingxia" sort="Feng, Mingxia" uniqKey="Feng M" first="Mingxia" last="Feng">Mingxia Feng</name>
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<author><name sortKey="Feng, Mingxia" sort="Feng, Mingxia" uniqKey="Feng M" first="Mingxia" last="Feng">Mingxia Feng</name>
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<author><name sortKey="He, Yong" sort="He, Yong" uniqKey="He Y" first="Yong" last="He">Yong He</name>
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<term>Animals</term>
<term>Antineoplastic Agents (pharmacology)</term>
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<term>Mice, Inbred BALB C</term>
<term>Protein Kinase Inhibitors (pharmacology)</term>
<term>RNA Interference</term>
<term>RNA, Small Interfering (genetics)</term>
<term>Retinal Dehydrogenase (biosynthesis)</term>
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<term>Xenograft Model Antitumor Assays</term>
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<term>Carcinome pulmonaire non à petites cellules (traitement médicamenteux)</term>
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<term>Dérivés de l'aniline (pharmacologie)</term>
<term>Facteurs de transcription SOX-B1 (biosynthèse)</term>
<term>Femelle</term>
<term>Humains</term>
<term>Inhibiteurs de protéines kinases (pharmacologie)</term>
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<term>Petit ARN interférent (génétique)</term>
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</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Beclin-1</term>
<term>ErbB Receptors</term>
<term>RNA, Small Interfering</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Acrylamides</term>
<term>Aniline Compounds</term>
<term>Antineoplastic Agents</term>
<term>Chloroquine</term>
<term>Protein Kinase Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Carcinome pulmonaire non à petites cellules</term>
<term>Tumeurs du poumon</term>
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<term>Lung Neoplasms</term>
</keywords>
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<term>Petit ARN interférent</term>
<term>Récepteurs ErbB</term>
<term>Résistance aux médicaments antinéoplasiques</term>
</keywords>
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<term>Lung Neoplasms</term>
</keywords>
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<term>Antinéoplasiques</term>
<term>Chloroquine</term>
<term>Dérivés de l'aniline</term>
<term>Inhibiteurs de protéines kinases</term>
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<term>Tumeurs du poumon</term>
</keywords>
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<term>Lignée cellulaire tumorale</term>
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<front><div type="abstract" xml:lang="en">Osimertinib, a third-generation epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI), shows great efficacy in EGFR-mutant non-small cell lung cancer (NSCLC); however, the resistance is inevitable. Osimertinib induces autophagy in NSCLC cells, but the role of autophagy in osimertinib resistance is not clear. We discovered that enhanced autophagy is associated with osimertinib resistance in vitro and in vivo. Inhibition of autophagy enhanced osimertinib cytotoxicity in both osimertinib-resistant and sensitive cells. Moreover, osimertinib-resistant cells exhibited stem cell-like properties, whereas autophagy inhibition decreased the stemness by downregulating the expression of SOX2 and ALDH1A1. Further, we found that knockdown of Beclin-1 inhibited the stem cell-like properties and restored osimertinib cytotoxicity. Osimertinib combined with chloroquine inhibited tumor growth more effectively than alone in xenograft mice. These results reveal that autophagy plays an adverse role in osimertinib cytotoxicity through inducing stem cell-like properties. Combination therapy of EGFR-TKI and autophagy inhibitor could provide a promising strategy to improve osimertinib cytotoxicity.</div>
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<affiliations><list><country><li>République populaire de Chine</li>
</country>
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<tree><country name="République populaire de Chine"><noRegion><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name>
</noRegion>
<name sortKey="Feng, Mingxia" sort="Feng, Mingxia" uniqKey="Feng M" first="Mingxia" last="Feng">Mingxia Feng</name>
<name sortKey="He, Yong" sort="He, Yong" uniqKey="He Y" first="Yong" last="He">Yong He</name>
<name sortKey="Hu, Chen" sort="Hu, Chen" uniqKey="Hu C" first="Chen" last="Hu">Chen Hu</name>
<name sortKey="Jiao, Lin" sort="Jiao, Lin" uniqKey="Jiao L" first="Lin" last="Jiao">Lin Jiao</name>
<name sortKey="Lin, Caiyu" sort="Lin, Caiyu" uniqKey="Lin C" first="Caiyu" last="Lin">Caiyu Lin</name>
<name sortKey="Lu, Conghua" sort="Lu, Conghua" uniqKey="Lu C" first="Conghua" last="Lu">Conghua Lu</name>
<name sortKey="Wang, Yubo" sort="Wang, Yubo" uniqKey="Wang Y" first="Yubo" last="Wang">Yubo Wang</name>
<name sortKey="Wu, Haiyan" sort="Wu, Haiyan" uniqKey="Wu H" first="Haiyan" last="Wu">Haiyan Wu</name>
<name sortKey="Ye, Junyi" sort="Ye, Junyi" uniqKey="Ye J" first="Junyi" last="Ye">Junyi Ye</name>
<name sortKey="Zhang, Dadong" sort="Zhang, Dadong" uniqKey="Zhang D" first="Dadong" last="Zhang">Dadong Zhang</name>
<name sortKey="Zhang, Kejun" sort="Zhang, Kejun" uniqKey="Zhang K" first="Kejun" last="Zhang">Kejun Zhang</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 000509 | SxmlIndent | more

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Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    ChloroquineV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     pubmed:30910592
   |texte=   Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer.
}}

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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:30910592" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a ChloroquineV1

This area was generated with Dilib version V0.6.33.
Data generation: Wed Mar 25 22:43:59 2020. Site generation: Sun Jan 31 12:44:45 2021

Serveur d'exploration Chloroquine

Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer.

Protective autophagy decreases osimertinib cytotoxicity through regulation of stem cell-like properties in lung cancer.

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	Serveur d'exploration Chloroquine
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.