Effects of letrozole on proliferation and apoptosis in cultured leiomyoma cells treated with prostaglandin E2

Objective: The objective was to determine the direct effect of letrozole on the proliferation and apoptosis of cultured leiomyoma cells cotreated with prostaglandin E-2 (PGE(2)). Study design: Leiomyoma cells were obtained from three groups of patients who had undergone hysterectomy due to leiomyoma. Percentages of antiproliferative cells were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed with sub-G1 cell counts by flow cytometry and Western blot analysis. Results: Combined treatment with 100 mu M letrozole and 10 mu M PGE2 for 48 h resulted in a significantly lower viability rate (25.9 +/- 14.5%) and an increased cell death rate (31.6 +/- 4.4%) than groups treated with letrozole or PGE2 alone. However, after adding 10 nM estradiol to the combined treatment group, the cell viability rate was restored (75.1 +/- 7.7%) and the cell death rate was decreased (10.5 +/- 3.1%). Increased caspase-3 expression was found in the letrozole and PGE2 combined treatment group, but not in the group in which estradiol was added. Conclusion: The present results demonstrate that letrozole inhibits growth and induces apoptosis of leiomyoma cells by blocking the aromatase up-regulated by PGE2 treatment. These findings support the need for further investigation of aromatase inhibitors as a medical treatment option in leiomyoma. (c) 2007 Elsevier Ireland Ltd. All rights reserved.