title: Leiomyoma fibrosis inhibited by liarozole, a retinoic acid metabolic blocking agent.
abstract: OBJECTIVE
  To study the influence of liarozole on leiomyoma cell proliferation and extracellular matrix (ECM) gene expression in immortalized leiomyoma cells.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  None.
  
  
  METHODS
  Tissue culture, real-time reverse transcription-polymerase chain reaction, Western blot.
  
  
  METHODS
  Proliferation, messenger RNA (mRNA), and ECM protein expression.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Gilden
authors.forename: Minnie
authors.initials: M
authors.lastname: Malik
authors.forename: Joy
authors.initials: J
authors.lastname: Britten
authors.forename: Tania
authors.initials: T
authors.lastname: Delgado
authors.forename: Gary
authors.initials: G
authors.lastname: Levy
authors.forename: William H
authors.initials: WH
authors.lastname: Catherino
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism*; D014212:Tretinoin / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D016326:Extracellular Matrix Proteins; D007093:Imidazoles; D014212:Tretinoin; C061121:liarozole