Background: Endometriosis (EMs) is a benign, but potential metastatic, gynecological disease. Our current study aims to examine whether all-trans retinoic acid (ATRA) inhibits the epithelial-to-mesenchymal transition (EMT) of endometriotic stromal stem cells, as well as to explore the mechanisms involved, especially the role of IL-6 played in.
Methods: Cell clonogenic capacity was examined by the low-density clonogenicity assay. Cell differentiation capacity was assessed by in vitro differentiation. The level of IL-6 was measured by the ELISA assay. Migration and invasion abilities were measured using the transwell assay. Western blot and RT-qPCR were performed to detect EMT-related genes and proteins.
Results: Large endometriotic stromal colony forming units (CFUs) could be regarded as the enrichment sets of endometriotic stromal stem cells. They maintained a higher potential for self-renewal, proliferation, invasion, and EMT, along with up-regulated IL-6. After ATRA treatment, the expression of IL-6 was significantly reduced, accompanied by a decrease in the migration, invasion, and EMT of large endometriotic stromal CFUs. In addition, the inhibition of ATRA was mediated by IL-6.
Conclusions: Our study showed that one of the therapeutic effects of ATRA on EMs through its modulation in EMT of large endometriotic stromal CFUs. ATRA may be a promising therapeutic strategy aimed at IL-6 for the stem-cell treatment of EMs.
Keywords: All-trans retinoic acid (ATRA); endometriosis (EMs); epithelial-to-mesenchymal transition (EMT); interleukin-6 (IL-6); stem cell.