Effects of letrozole on proliferation and apoptosis in cultured leiomyoma cells treated with prostaglandin E(2).
OBJECTIVE
The objective was to determine the direct effect of letrozole on the proliferation and apoptosis of cultured leiomyoma cells co-treated with prostaglandin E(2) (PGE(2)).


METHODS
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 microM letrozole and 10 microM PGE(2) 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 PGE(2) alone. However, after adding 10nM 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 PGE(2) combined treatment group, but not in the group in which estradiol was added.


CONCLUSIONS
The present results demonstrate that letrozole inhibits growth and induces apoptosis of leiomyoma cells by blocking the aromatase up-regulated by PGE(2) treatment. These findings support the need for further investigation of aromatase inhibitors as a medical treatment option in leiomyoma.
Han
Myoungseok
M
Department of Obstetrics and Gynecology, College of Medicine, Dong-A University, Busan, South Korea. hmsobgy@dau.ac.kr
Kim
Ji Young
JY
Park
Ji-Eun
JE
Kim
Jong-Min
JM
Lee
Kyu-Sup
KS
D017209:Apoptosis / Q000187:drug effects*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007889:Leiomyoma / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D020536:Enzyme Activators; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; D015232:Dinoprostone