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

ObjectiveThe objective was to determine the direct effect of letrozole on the proliferation and apoptosis of cultured leiomyoma cells co-treated with prostaglandin E2 (PGE2).Study designLeiomyoma 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.ResultsCombined treatment with 100 μM letrozole and 10 μM PGE2 for 48 h resulted in a significantly lower viability rate (25.9 ± 4.5%) 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.ConclusionThe 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.