Your browser doesn't support javascript.
loading
Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high-fat diet.
Miura, Kouichi; Ohnishi, Hirohide; Morimoto, Naoki; Minami, Shinichiro; Ishioka, Mitsuaki; Watanabe, Shunji; Tsukui, Mamiko; Takaoka, Yoshinari; Nomoto, Hiroaki; Isoda, Norio; Yamamoto, Hironori.
Afiliación
  • Miura K; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Ohnishi H; Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
  • Morimoto N; Japan Organization of Occupational Health and Safety, Kanagawa, Japan.
  • Minami S; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Ishioka M; Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.
  • Watanabe S; Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan.
  • Tsukui M; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Takaoka Y; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Nomoto H; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Isoda N; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Yamamoto H; Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Cancer Sci ; 110(2): 771-783, 2019 Feb.
Article en En | MEDLINE | ID: mdl-30520543
Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH-mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH-related liver cirrhosis and HCC. In the present study, a steatohepatitis-related HCC model, hepatocyte-specific phosphatase and tensin homolog (Pten)-deficient (PtenΔhep ) mice were fed a high-fat (HF) diet with/without ezetimibe. In the standard-diet group, ezetimibe did not reduce the development of liver tumors in PtenΔhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF-positive cells and vascular endothelial cells in the tumors of PtenΔhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in PtenΔhep mice on the HF diet. Tumor cells were highly proliferative with HF-diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in PtenΔhep mice with hypercholesterolemia.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Angiogénesis / Dieta Alta en Grasa / Ezetimiba / Neoplasias Hepáticas / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cancer Sci Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de la Angiogénesis / Dieta Alta en Grasa / Ezetimiba / Neoplasias Hepáticas / Neovascularización Patológica Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cancer Sci Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido