Selective blockade of prostaglandin E 2 receptors EP2 and EP4 signaling inhibits proliferation of human endometriotic epithelial cells and stromal cells through distinct cell cycle arrest

To determine interactions between prostaglandin (PG) E 2 signaling and proliferation of endometriotic cells to increase our knowledge about PGE 2 signaling in the pathogenesis of endometriosis in humans. Immortalized human endometriotic epithelial and stromal cells were used as an in vitro model. Effects of inhibition of PGE 2 receptors on proliferation of endometriotic cells and associated cell cycle regulation were determined. College Veterinary Medicine and Biomedical Sciences, Texas A&M University. Not available. None. Cell proliferation, cell viability, cell cycle, regulation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors. Selective blockade of EP2/EP4 inhibited proliferation of human endometriotic cells by inducing cell cycle arrest at the G 1 –S and G 2 –M checkpoints in epithelial cells and at the G 2 –M checkpoint in stromal cells. This cell cycle arrest during specific checkpoints was associated with distinct regulation of respective cyclins and cyclin-dependent kinases. Inhibition of EP1 did not decrease endometriotic cell proliferation. For the first time data from the present study provide a direct molecular link between PGE 2 signaling and proliferation of endometriotic cells and suggest that inhibition of EP2/EP4 could be a potential nonestrogen (E) treatment option for endometriosis in women.