PPAR-gamma activation inhibits proliferation of endometriotic epithelial and stromal cells and is pro-apoptotic in endometriotic stromal cells in vitro

Abstract

OBJECTIVE: The PPAR-gamma ligand, ciglitazone (CIG), has been shown to decrease aromatase levels in endometriotic epithelial and stromal cell lines. Dose-response experiments showed CIG 20 μM to be ideal; endometriotic cell number decreased in a dose-dependent manner. We sought to determine if the decrease in endometriotic cell number was due to antiproliferative (CDK2, CDK4) and/or apoptotic (caspase-3) effects. DESIGN: In vitro study using the immortalized human endometriotic stromal cell line 22B and epithelial cell line 12Z. MATERIALS AND METHODS: Endometriotic cells were cultured and subsequently treated with CIG x 24 hours. Treatment groups (n=3 for each experiment) consisted of control (no CIG) compared to CIG at 20 μM. Western blot was performed to assess effects of CIG on CDK2, CDK4, and caspase-3. Comparisons between treatment groups were made using a one-way ANOVA followed by post-hoc comparison of means. RESULTS: Activation of PPAR-gamma using CIG 20 μM decreased expression of CDK2 and CDK4 proteins in the endometriotic stromal cells 22B 4-fold (P < 0.05) and in the endometriotic epithelial cells 12Z 1-fold; CIG 20 μM cleaved caspase-3 protein in 22B (P < 0.05) but not in 12Z cells. CONCLUSION: In the endometriotic epithelial cell type, CIG did not induce apoptosis but did dysregulate cell cycle machinery. In contrast, in the endometriotic stromal cell type, CIG induced both apoptosis and cell cycle deregulation.