Combining Nelfinavir With Chloroquine Inhibits
Nelfinavir
chloroquine
non-small cell lung cancer
proteotoxicity
Journal
In vivo (Athens, Greece)
ISSN: 1791-7549
Titre abrégé: In Vivo
Pays: Greece
ID NLM: 8806809
Informations de publication
Date de publication:
Historique:
received:
06
11
2020
revised:
26
11
2020
accepted:
27
11
2020
entrez:
6
1
2021
pubmed:
7
1
2021
medline:
22
6
2021
Statut:
ppublish
Résumé
Nelfinavir is a human immunodeficiency virus protease inhibitor that is currently being repositioned as an anticancer drug. Chloroquine, an anti-malarial lysosomotropic drug, inhibits autophagy. It has been reported that the combination of nelfinavir and chloroquine significantly enhances endoplasmic reticulum (ER) stress and induces selective cell death in multiple cell line models (in vitro). We assessed the effects of the combination of these drugs on human NSCLC cell lines in vitro using cell proliferation assay and performed preclinical treatment studies using cell line-derived xenograft mouse models in vivo. In vitro, this combination enhanced inhibition of NSCLC cell proliferation with increased proteotoxicity, including ER stress, and apoptosis. In vivo, the growth of human NSCLC xenograft tumors was inhibited, which correlated with increased apoptosis and induction of ER stress as well as NSCLC growth in vitro. Our findings suggest that the induction of proteotoxicity provides a promising new target for developing anticancer drugs.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Nelfinavir is a human immunodeficiency virus protease inhibitor that is currently being repositioned as an anticancer drug. Chloroquine, an anti-malarial lysosomotropic drug, inhibits autophagy. It has been reported that the combination of nelfinavir and chloroquine significantly enhances endoplasmic reticulum (ER) stress and induces selective cell death in multiple cell line models (in vitro).
MATERIALS AND METHODS
METHODS
We assessed the effects of the combination of these drugs on human NSCLC cell lines in vitro using cell proliferation assay and performed preclinical treatment studies using cell line-derived xenograft mouse models in vivo.
RESULTS
RESULTS
In vitro, this combination enhanced inhibition of NSCLC cell proliferation with increased proteotoxicity, including ER stress, and apoptosis. In vivo, the growth of human NSCLC xenograft tumors was inhibited, which correlated with increased apoptosis and induction of ER stress as well as NSCLC growth in vitro.
CONCLUSION
CONCLUSIONS
Our findings suggest that the induction of proteotoxicity provides a promising new target for developing anticancer drugs.
Identifiants
pubmed: 33402459
pii: 35/1/141
doi: 10.21873/invivo.12241
pmc: PMC7880743
doi:
Substances chimiques
Chloroquine
886U3H6UFF
Nelfinavir
HO3OGH5D7I
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
141-145Informations de copyright
Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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