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

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Romidepsin treatment inhibited transcription, expression, and secretion of vascular epithelial growth factor (VEGF) in human epithelial endometriotic cells.

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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-1α (HIF-1α), 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.

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Condition tags

endometriosis

MeSH descriptors

Depsipeptides Endometriosis Epithelial Cells Peritoneal Diseases Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factor A Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Antibiotics, Antineoplastic Antibiotics, Antineoplastic Antibiotics, Antineoplastic Cell Line, Transformed Cell Line, Transformed Depsipeptides Depsipeptides Dose-Response Relationship, Drug Dose-Response Relationship, Drug Down-Regulation Down-Regulation

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europepmc
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openalex
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pubmed
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