Overexpression of AGR2 Is Associated With Drug Resistance in Mutant Non-small Cell Lung Cancers.
Apoptosis
/ drug effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Movement
/ genetics
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Drug Resistance, Neoplasm
/ genetics
ErbB Receptors
/ antagonists & inhibitors
Erlotinib Hydrochloride
/ pharmacology
Gefitinib
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Mucoproteins
/ genetics
Mutation
Neoplasm Invasiveness
/ genetics
Oncogene Proteins
/ genetics
Protein Kinase Inhibitors
/ pharmacology
Quinazolines
/ pharmacology
ADAMTS6
AGR2
NSCLC
gefitinib resistance
mutant NSCLC
yuanhuadine
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
09
02
2020
revised:
18
02
2020
accepted:
19
02
2020
entrez:
3
4
2020
pubmed:
3
4
2020
medline:
10
4
2020
Statut:
ppublish
Résumé
The resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib or erlotinib, is considered a major challenge in the treatment of patients with non-small cell lung cancer (NSCLC). Herein, we identified the critical roles of anterior gradient 2 (AGR2) in gefitinib (Gef) resistance of mutant NSCLC cells. Using datasets from a pair of NSCLC-sensitive and NSCLC-resistant cells, immunoblotting, immunofluorescence and immunohistochemistry, and cell viability assays were applied to identify the effects of AGR2. AGR2 was found to be significantly over-expressed in Gef-resistant cells and was highly associated with drug resistance, proliferation, migration, and invasion of cancer cells. Moreover, AGR2 and ADAMTS6 formed a negative feedback loop in drug-resistant cells. Modulation of overexpression of AGR2 in mutant NSCLC cells may be an attractive therapeutic strategy for the treatment of EGFR-TKI-resistant NSCLC.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
The resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib or erlotinib, is considered a major challenge in the treatment of patients with non-small cell lung cancer (NSCLC). Herein, we identified the critical roles of anterior gradient 2 (AGR2) in gefitinib (Gef) resistance of mutant NSCLC cells.
MATERIALS AND METHODS
METHODS
Using datasets from a pair of NSCLC-sensitive and NSCLC-resistant cells, immunoblotting, immunofluorescence and immunohistochemistry, and cell viability assays were applied to identify the effects of AGR2.
RESULTS
RESULTS
AGR2 was found to be significantly over-expressed in Gef-resistant cells and was highly associated with drug resistance, proliferation, migration, and invasion of cancer cells. Moreover, AGR2 and ADAMTS6 formed a negative feedback loop in drug-resistant cells.
CONCLUSION
CONCLUSIONS
Modulation of overexpression of AGR2 in mutant NSCLC cells may be an attractive therapeutic strategy for the treatment of EGFR-TKI-resistant NSCLC.
Identifiants
pubmed: 32234873
pii: 40/4/1855
doi: 10.21873/anticanres.14139
doi:
Substances chimiques
AGR2 protein, human
0
Mucoproteins
0
Oncogene Proteins
0
Protein Kinase Inhibitors
0
Quinazolines
0
Erlotinib Hydrochloride
DA87705X9K
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Gefitinib
S65743JHBS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1855-1866Informations de copyright
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.