NAG-1 expression and apoptosis induction in endometrial stromal cells of patients with endometriosis by histone deacetylase inhibitor trichostatin A

Abstract

Objective

The present study investigated the effects of trichostatin A (TSA) on non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) expression and apoptosis in human endometrial stromal cells (HESCs) and assessed whether these effects are enhanced in the presence of 5-aza-2''-deoxycytidine (5-aza-dC).

Methods

Eutopic endometrial tissue samples were obtained from 10 patients with fibroids who underwent hysterectomy. Ectopic endometrial tissues were obtained from 15 patients with endometriotic cysts who underwent cystectomy. HESCs were isolated and cultured with different concentrations of TSA. Real-time PCR and western blotting were used to evaluate NAG-1 mRNA and protein levels, respectively. Apoptosis was assessed by flow cytometry.

Results

TSA induced NAG-1 expression and apoptosis in HESCs. Gene knockdown experiments using small interfering RNA confirmed an association between NAG-1 expression and TSA-induced apoptosis. We did not observe synergy in the apoptosis-inducing effects of TSA and 5-aza-dC in HESCs.

Conclusion

TSA induced apoptosis in HESCs via induction of NAG-1 expression. These results suggest that TSA-and possibly other HDACIs or agents that induce NAG-1 expression-can be effective for treating endometriosis.