VEGF-mediated cell survival in non-small-cell lung cancer: implications for epigenetic targeting of VEGF receptors as a therapeutic approach.

Abstract

AIMS:

To evaluate the potential therapeutic utility of histone deacetylase inhibitors (HDACi) in targeting VEGF receptors in non-small-cell lung cancer.

MATERIALS & METHODS:

Non-small-cell lung cancer cells were screened for the VEGF receptors at the mRNA and protein levels, while cellular responses to various HDACi were examined.

RESULTS:

Significant effects on the regulation of the VEGF receptors were observed in response to HDACi. These were associated with decreased secretion of VEGF, decreased cellular proliferation and increased apoptosis which could not be rescued by addition of exogenous recombinant VEGF. Direct remodeling of the VEGFR1 and VEGFR2 promoters was observed. In contrast, HDACi treatments resulted in significant downregulation of the Neuropilin receptors.

CONCLUSION:

Epigenetic targeting of the Neuropilin receptors may offer an effective treatment for lung cancer patients in the clinical setting.

• Authors: Martin P Barr, Kenneth J O'Byrne, Nael Al-Sarraf, Steven G Gray
• Journal: Epigenomics (Epigenomics) Vol. 7 Issue 6 Pg. 897-910 ( 2015) ISSN: 1750-192X [Electronic] England
• PMID: 26479311 (Publication Type: Journal Article)

Chemical References

• Histone Deacetylase Inhibitors
• Histones
• Hydroxamic Acids
• Vascular Endothelial Growth Factor A
• trichostatin A
• Vorinostat
• Receptors, Vascular Endothelial Growth Factor

Topics

• Acetylation
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (genetics)
• Chromatin Assembly and Disassembly (genetics)
• Epigenesis, Genetic (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylase Inhibitors (pharmacology)
• Histones (metabolism)
• Humans
• Hydroxamic Acids (pharmacology)
• Lung Neoplasms (drug therapy, genetics, metabolism)
• Molecular Targeted Therapy
• Receptors, Vascular Endothelial Growth Factor (genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vorinostat