Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin

Abstract

Objective: To investigate whether the histone deacetylase (HDAC) inhibitor romidepsin down-regulates VEGF (vascular endothelial growth factor) gene expression and abrogates VEGF protein secretion in human epithelial endometriotic cells. Design: In vitro study with human immortalized epithelial endometriotic cells. Setting: University hospital. Patient(s): Not applicable. Intervention(s): None.
Main Outcome Measure(s): Real-time reverse-transcriptase polymerase chain reaction to evaluate VEGF gene expression, immunoblot analysis to evaluate protein expression, and enzyme-linked immunosorbent assay to evaluate VEGF protein secretion into the culture medium. Result(s): Treatment of 11z human endometriotic cells with romidepsin statistically significantly inhibited VEGF gene transcription and down-regulated VEGF protein expression. Moreover, romidepsin abrogated the secretion of VEGF protein into the culture medium. Romidepsin also reduced the expression of hypoxia-inducible factor-1a (HIF-1a), which is implicated in the transcription of the VEGF gene, in cobalt chloride-pretreated (to mimic hypoxic conditions) 11z cultures.
Conclusion(s): Romidepsin targets VEGF at the transcriptional level, which subsequently leads to the reduction of secreted VEGF (the ‘‘active’’ form of VEGF). Therefore, romidepsin may be a potential therapeutic candidate against angiogenesis in endometriosis.