Emodin Reverses the Epithelial-Mesenchymal Transition of Human Endometrial Stromal Cells by Inhibiting ILK/GSK-3β Pathway.

Abstract

PurposeTo explore the exact mechanism through which emodin down-regulates the migration and invasion abilities of endometrial stromal cells. Moreover, to explore the theoretical basis of emodin in the treatment of endometriosis.Patients and MethodsEndometriosis endometrial stromal cells (EESs) were cultured from 15 women with endometriosis and control endometrial stromal cells (CESs) were cultured from 12 women without endometriosis. The levels of proteins were evaluated by Western blot. The migration and invasion abilities of cells were detected by transwell assays.ResultsThe abilities of migration and invasion of EESs were much stronger than those of CESs. After treated with emodin, the migration and invasion abilities of EESs and CESs were significantly down-regulated, and the levels of integrin-linked kinase (ILK) and p-GSK-3β were statistically down-regulated in EESs. Besides that, the expression of keratin was up-regulated while the expression of vimentin, β-catenin and slug were all down-regulated by emodin in a dose- and time-dependent manner. Silencing of ILK gene in EESs also achieved the above effects, which were strengthened by emodin. Conversely, exogenous expression of ILK in CESs increased the expression of p-GSK-3β, which were abrogated by emodin. Furthermore, SB216763 increased migration and invasion abilities of CESs by facilitating the epithelial–mesenchymal transition (EMT) through up-regulating levels of p-GSK-3β, β-catenin and slug, which were also abrogated by emodin.ConclusionEmodin inhibits the migration and invasion abilities of human endometrial stromal cells by reversing the EMT via ILK/GSK-3β pathway. So, emodin may be considered as a promising targeted therapy for endometriosis.