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  • Title: Pyrrolidine dithiocarbamate attenuates nuclear factor-ĸB activation, cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic epithelial cells.
    Author: Zhang JJ, Xu ZM, Chang H, Zhang CM, Dai HY, Ji XQ, Li C, Wang XF.
    Journal: Gynecol Obstet Invest; 2011; 72(3):163-8. PubMed ID: 21968252.
    Abstract:
    BACKGROUND: The nuclear factor-κB (NF-κB) 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-κB inhibitor, in the treatment of endometriosis. METHODS: The phosphorylation of IκB, expression of nuclear p65 protein and NF-κB 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-α (TNF-α) showed stronger inhibitory effects on IκB phosphorylation, expression of nuclear p65 protein and NF-κB DNA-binding activity in EECs than in EuECs or NECs. Pretreatment of EECs with PDTC resulted in a dose-dependent reduction in the TNF-α-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.
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