Liarozole inhibits transforming growth factor-?3--mediated extracellular matrix formation in human three-dimensional leiomyoma cultures.

ABSTRACT: OBJECTIVE:To investigate the impact of liarozole on transforming growth factor-?3 (TGF-?3) expression, TGF-?3 controlled profibrotic cytokines, and extracellular matrix formation in a three-dimensional (3D) leiomyoma model system. DESIGN:Molecular and immunohistochemical analysis in a cell line evaluated in a three-dimensional culture. SETTING:Laboratory study. PATIENT(S):None. INTERVENTION(S):Treatment of leiomyoma and myometrial cells with liarozole and TGF-?3 in a three-dimensional culture system. MAIN OUTCOME MEASURE(S):Quantitative real-time reverse-transcriptase polymerase chain reaction and Western blotting to assess fold gene and protein expression of TGF-?3 and TGF-?3 regulated fibrotic cytokines: collagen 1A1 (COL1A1), fibronectin, and versican before and after treatment with liarozole, and confirmatory immunohistochemical stains of treated three-dimensional cultures. RESULT(S):Both TGF-?3 gene and protein expression were elevated in leiomyoma cells compared with myometrium in two-dimensional and 3D cultures. Treatment with liarozole decreased TGF-?3 gene and protein expression. Extracellular matrix components versican, COL1A1, and fibronectin were also decreased by liarozole treatment in 3D cultures. Treatment of 3D cultures with TGF-?3 increased gene expression and protein production of COL1A1, fibronectin, and versican. CONCLUSION(S):Liarozole decreased TGF-?3 and TGF-?3-mediated extracellular matrix expression in a 3D uterine leiomyoma culture system.

SUBMITTER: Levy G 

PROVIDER: S-EPMC4152900 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature