Martin P Barr1, Kenneth J O'Byrne1,2, Nael Al-Sarraf1, Steven G Gray1. 1. Thoracic Oncology Research Group, School of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital & Trinity College Dublin, Dublin 8, Ireland. 2. Cancer & Ageing Research Program, Queensland University of Technology, Brisbane, Australia.
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.
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 cancerpatients in the clinical setting.