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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4504 - Role of Pioglitazone on gene/protein expression profile, bioenergetics and TGF_/SMAD signaling pathway in NSCLC

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Raimondo Di Liello

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

R. Di Liello, G. Viscardi, V. Ciaramella, G. Barra, G. Esposito, M. Fasano, F. Ciardiello, F. Morgillo

Author affiliations

  • Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Napoli/IT
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Resources

Abstract 4504

Background

Pioglitazone is an antidiabetic drug of the Thiazolidinediones (TZDs) class that acts as ligand for PPAR-γ, a member of peroxisome proliferator activated receptors (PPARs), that regulates lipid and glucose cell metabolism. Prior studies in in vitro and in vivo models of non-small cell lung cancer (NSCLC) showed that PPAR-γ modulation affects cancer cells proliferation and differentiation but few reported studies have investigated molecular pathways involved in the potential role of PPAR-γ agonists as anti-cancer agents.

Methods

NSCLC cell lines H460 and H1299, were treated with different doses of Pioglitazone. Anti-proliferative effect was determined by MTT, colony-forming assay and flow-cytometry. Protein expression was detected by Western Blot analysis while functional mitochondrial measurements were performed with SeaHorse© stress test. Finally, cell lines samples were analyzed with a cDNA microarray assay.

Results

Pioglitazone significantly reduces cell proliferation and invasion with an IC50 of 1-5 µM. Analysis of apoptosis confirmed the data. Western blot analysis demonstrated a dose-related reduction of Survivin and phosphorylated proteins of MAP kinase pathway and cDNA microarray expression profiling showed a down-regulation of MAPK, Myc and RAS genes. Oxygen Consumption Rate (OCR) and proportional Glut-1 protein expression reduction of treated cells demonstrated cell bioenergetics modulation. Interestingly cDNA microarray analysis showed that also TGFβ pathway is regulated by Pioglitazione through pTGFβR1 and pSMAD3 down-regulation and consecutive up-regulation of total TGFβR1.

Conclusions

Pioglitazone regulates NSCLC cell lines proliferation and bioenergetics. Moreover, affecting TGFβ/SMAD signaling pathway, it could have a role in epitelial-to-mesenchymal transition (EMT) and cancer invasive phenotype development. These results encourage the study of PPAR-γ agonists as anti-cancer agents and promote research to explore the mechanisms beyond their activity in NSCLC models.

Clinical trial identification

Legal entity responsible for the study

Università degli Studi della Campania “Luigi Vanvitelli”.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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