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Leiomyoma fibrosis inhibited by liarozole, a retinoic acid metabolic blocking agent
Melissa Gilden1, Minnie Malik, Joy Britten
1Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
Objective:
To study the influence of liarozole on leiomyoma cell proliferation and extracellular matrix (ECM) gene expression in immortalized leiomyoma cells.
Design:
Laboratory study.
Setting:
University hospital.
Patient(S):
None.
Intervention(S):
Tissue culture, real-time reverse transcription-polymerase chain reaction, Western blot.
Main Outcome Measure(S):
Proliferation, messenger RNA (mRNA), and ECM protein expression.
Result(S):
Proliferation of leiomyoma cells was inhibited by treatment with liarozole at suprapharmacologic concentrations. The mRNA and protein expression of COL1A1, COL4A2, versican, fibromodulin, and fibronectin was increased in untreated leiomyoma cells compared with untreated patient-matched myometrial cells. Extracellular matrix mRNA expression was decreased in a dose-dependent manner in leiomyoma cells treated with pharmacologic concentrations of liarozole. In addition, myometrial cells treated with liarozole demonstrated no statistically significant alteration in ECM regulation.
Conclusion(S):
Liarozole inhibited ECM protein production at pharmacologic concentrations in immortalized human leiomyoma cells. Retinoic acid metabolic blocking agents represent a potential therapeutic drug family for human leiomyomas.