Pyrrolidine dithiocarbamate attenuates nuclear factor-kB activation, cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic epithelial cells.

摘要

BACKGROUND: The nuclear factor-kappaB (NF-kappaB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. We sought to examine the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-kappaB inhibitor, in the treatment of endometriosis. METHODS: The phosphorylation of IkappaB, expression of nuclear p65 protein and NF-kappaB DNA binding in endometriotic epithelial cells (EECs), endometriotic eutopic epithelial cells (EuECs) and normal epithelial cells (NECs) were detected by Western blot analysis and electrophoretic mobility shift assay. Cyclooxgenase-2 (COX-2) gene and protein expressions in EECs were measured by RT-PCR and Western blot analysis. Prostaglandin E(2) (PGE(2)) production of EECs was measured by ELISA. RESULTS: PDTC in the absence or presence of tumor necrosing factor-alpha (TNF-alpha) showed stronger inhibitory effects on IkappaB phosphorylation, expression of nuclear p65 protein and NF-kappaB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-alpha-induced expressions of COX-2 at gene and protein levels, as well as a reduction of PGE(2) synthesis. CONCLUSION: PDTC may represent a novel therapeutic strategy for treatment of endometriosis.