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

Imesch P, Patrick Imesch, Samartzis EP, Eleftherios Pierre Samartzis, Eleftherios P Samartzis, Schneider M, Michael Schneider, Fink D, Daniel Fink, André Fedier
Fertility and sterility · 2011 · vol. 95(5) , pp. 1579–1583 · doi:10.1016/j.fertnstert.2010.12.058 · PMID:21295294 · W2102610819
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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

ObjectiveTo 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.DesignIn vitro study with human immortalized epithelial endometriotic cells.SettingUniversity 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 Antibiotics, Antineoplastic Antibiotics, Antineoplastic Cell Line, Transformed Depsipeptides Dose-Response Relationship, Drug Down-Regulation Down-Regulation Down-Regulation Drug Evaluation, Preclinical Endometriosis Endometriosis Endometriosis

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