Peroxisome proliferator-activated receptor-gamma and retinoid X receptor agonists synergistically suppress proliferation of immortalized endometrial stromal cells

ObjectiveTo examine whether trichostatin A (TSA), a histone deacetylase inhibitor (HDACI), can induce up-regulation of proxisome proliferator-activating receptor γ (PPARγ) and to see whether LG100268, a retinoid X receptor (RXR) ligand, can inhibit proliferation of endometriotic cells alone or in synergy with ciglitazone, a PPARγ agonist.DesignOne endometrial stromal cell line and two endometriotic cell lines used as a model system: Western blot analysis to determine whether TSA can up-regulate PPARγ expression, and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) proliferation assay to see whether ciglitazone and LG100268 have any antiproliferative effects individually or jointly.SettingAcademic.Patient(s)None.Intervention(s)Culture of immortalized endometrial and endometriotic cell lines with TSA, or ciglitazone or LG100268.Main Outcome Measure(s)PPARγ protein expression levels in cells treated with or without TSA, and number of viable cells treated with or without ciglitazone, LG100268, or both.Result(s)The TSA treatment resulted in up-regulation of PPARγ expression in all cell lines in a dose-dependent fashion. Both ciglitazone and LG100268 inhibited proliferation in a dose-dependent manner, and the antiproliferative effects appeared to be synergistic. In addition, endometriotic cells were more sensitive than endometrial stromal cells to LG100268 treatment.Conclusion(s)The up-regulation of PPARγ induced by TSA indicates that the action of HDACIs also includes the PPARγ signaling pathway, suggesting that the activation of PPARγ is a desirable way to contain endometriosis phenotypes. The higher sensitivity of endometriotic cells than their endometrial counterpart to LG100268 treatment suggests that the sensitivity differential could be exploited effectively to eradicate unwanted ectopic endometrial tissues while minimizing the collateral damage to the normal endometrial tissues.