Simvastatin induces degradation of the extracellular matrix in human leiomyomata: novel in vitro, in vivo, and patient level evidence of matrix metalloproteinase involvement.
F S Sci
; 5(1): 80-91, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38043603
ABSTRACT
OBJECTIVES:
To assess the effect of simvastatin on uterine leiomyoma growth and extracellular matrix (ECM) deposition.DESIGN:
Laboratory analysis of human leiomyoma cell culture, xenograft in a mouse model, and patient tissue from a clinical trial.SETTING:
Academic research center. PATIENT(S) Tissue culture from human leiomyoma tissue and surgical leiomyoma tissue sections from a placebo-controlled randomized clinical trial. INTERVENTION(S) Simvastatin treatment. MAIN OUTCOME MEASURE(S) Serum concentrations, xenograft volumes, and protein expression.RESULTS:
Mice xenografted with 3-dimensional human leiomyoma cultures were divided as follows 7 untreated controls; 12 treated with activated simvastatin at 10 mg/kg body weight; and 15 at 20 mg/kg body weight. Simvastatin was detected in the serum of mice injected at the highest dose. Xenograft volumes were significantly smaller (mean 53% smaller at the highest concentration). There was dissolution of compact ECM, decreased ECM formation, and lower collagen protein expression in xenografts. Membrane type 1 matrix metalloproteinase was increased in vitro and in vivo. Matrix metalloproteinase 2 and low-density lipoprotein receptor-related protein 1 were increased in vitro.CONCLUSIONS:
Simvastatin exhibited antitumoral activity with ECM degradation and decreased leiomyoma tumor volume in vivo. Activation of the matrix metalloproteinase 2, membrane type 1 matrix metalloproteinase, and low-density lipoprotein receptor-related protein 1 pathway may explain these findings.Palavras-chave
Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Uterinas
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Leiomioma
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
F S Sci
Ano de publicação:
2024
Tipo de documento:
Article