Activity and molecular targets of pioglitazone via blockade of proliferation, invasiveness and bioenergetics in human NSCLC.
A549 Cells
Adenocarcinoma of Lung
/ drug therapy
Apoptosis
/ drug effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Glucose
/ metabolism
Humans
Mitogen-Activated Protein Kinase Kinases
/ genetics
Neoplasm Invasiveness
/ genetics
PPAR gamma
/ agonists
Pioglitazone
/ pharmacology
Receptor, Transforming Growth Factor-beta Type I
/ genetics
Signal Transduction
/ genetics
Smad3 Protein
/ genetics
Transforming Growth Factor beta1
/ genetics
Bioenergetics
EMT
Glitazones
Lung cancer
Metabolism
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
26 Apr 2019
26 Apr 2019
Historique:
received:
11
01
2019
accepted:
14
04
2019
entrez:
28
4
2019
pubmed:
28
4
2019
medline:
5
9
2019
Statut:
epublish
Résumé
Pioglitazone, a synthetic peroxisome proliferator activated receptor (PPAR-γ) ligand, is known as an antidiabetic drug included in the thiazolidinediones (TZDs) class. It regulates the lipid and glucose cell metabolism and recently a role in the inhibition of numerous cancer cell processes has been described. In our work we investigate the anti-tumor effects of pioglitazone in in vitro models of non small cell lung cancer (NSCLC) and also, we generated ex-vivo three-dimensional (3D) cultures from human lung adenocarcinoma (ADK) as a model to test drug efficacy observed in vitro. The inhibitory effect of pioglitazone on cell proliferation, apoptosis and cell invasion in a panel of human NSCLC cell lines was evaluated by multiple assays. Pioglitazone reduced proliferative and invasive abilities with an IC Data indicate that PPAR-γ agonists represent an attractive treatment tool and by suppression of cell growth (in vitro and ex vivo models) and of invasion via blockade of MAPK cascade and TGFβ/SMADs signaling, respectively, and its role in cancer bioenergetics and metabolism indicate that PPAR-γ agonists represent an attractive treatment tool for NSCLC.
Sections du résumé
BACKGROUND
BACKGROUND
Pioglitazone, a synthetic peroxisome proliferator activated receptor (PPAR-γ) ligand, is known as an antidiabetic drug included in the thiazolidinediones (TZDs) class. It regulates the lipid and glucose cell metabolism and recently a role in the inhibition of numerous cancer cell processes has been described.
METHODS
METHODS
In our work we investigate the anti-tumor effects of pioglitazone in in vitro models of non small cell lung cancer (NSCLC) and also, we generated ex-vivo three-dimensional (3D) cultures from human lung adenocarcinoma (ADK) as a model to test drug efficacy observed in vitro. The inhibitory effect of pioglitazone on cell proliferation, apoptosis and cell invasion in a panel of human NSCLC cell lines was evaluated by multiple assays.
RESULTS
RESULTS
Pioglitazone reduced proliferative and invasive abilities with an IC
CONCLUSIONS
CONCLUSIONS
Data indicate that PPAR-γ agonists represent an attractive treatment tool and by suppression of cell growth (in vitro and ex vivo models) and of invasion via blockade of MAPK cascade and TGFβ/SMADs signaling, respectively, and its role in cancer bioenergetics and metabolism indicate that PPAR-γ agonists represent an attractive treatment tool for NSCLC.
Identifiants
pubmed: 31027492
doi: 10.1186/s13046-019-1176-1
pii: 10.1186/s13046-019-1176-1
pmc: PMC6485164
doi:
Substances chimiques
PPAR gamma
0
SMAD3 protein, human
0
Smad3 Protein
0
TGFB1 protein, human
0
Transforming Growth Factor beta1
0
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
TGFBR1 protein, human
EC 2.7.11.30
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Glucose
IY9XDZ35W2
Pioglitazone
X4OV71U42S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
178Références
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