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Therapeutic potential of endothelin inhibitors in canine hemangiosarcoma.
Fukumoto, Shinya; Saida, Kaname; Sakai, Hiroki; Ueno, Hiroshi; Iwano, Hidetomo; Uchide, Tsuyoshi.
Afiliación
  • Fukumoto S; Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
  • Saida K; Institute for Biomedical Research, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
  • Sakai H; Veterinary Pathology, Joint Department of Veterinary Medicine, Gifu University, Gifu 501-1112, Japan.
  • Ueno H; Veterinary Surgery, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
  • Iwano H; Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
  • Uchide T; Department of Veterinary Surgery, Faculty of Veterinary Medicine, Tokyo University of Agriculture and Technology (TUAT), Fuchu, Tokyo 183-8509, Japan. Electronic address: uchide@cc.tuat.ac.jp.
Life Sci ; 159: 55-60, 2016 Aug 15.
Article en En | MEDLINE | ID: mdl-26835989
AIMS: Hemangiosarcoma (HSA) that originates from vascular endothelial cells is the most common splenic malignant neoplasm in dogs, as it accounts for approximately 20% of all canine soft tissue sarcomas. In this study, inhibitory effects of endothelin receptor antagonists on the growth of HSA cells were examined using cell lines established from canine HSA. MAIN METHODS: The preproendothelin-1 (PPET-1), endothelin type A receptor (ETA) and endothelin type B receptor (ETB) mRNA expression levels in HSA cell lines (n=5) were analyzed quantitatively by real-time RT-PCR. These levels were compared with those in HSA tissues (n=11) and those in normal splenic tissues (n=6). ETA and ETB protein expression was examined by western blot. The production and secretion of endothelin-1 (ET-1) and big ET-1 by cell lines were analyzed by measuring the levels in the culture medium by ELISA. The inhibitory effects of endothelin receptor antagonists (ambrisentan, BQ788 and bosentan) on cell growth were evaluated by WST-8 assay. KEY FINDINGS: The PPET1 and ETA mRNA expression levels were elevated in HSA tissues and HSA cell lines compared with normal tissues. In cell lines, the production of ET-1 and big ET-1 peptide as well as the expression of ETA protein were detected, but the levels of ETB were not measured. Ambrisentan and bosentan inhibited growth activity in cell lines. Ambrisentan was more effective than bosentan. SIGNIFICANCE: These findings demonstrate the importance of the ETA axis in canine HSA as well as the potential of ETA inhibitors in the treatment of canine HSA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Enfermedades de los Perros / Antagonistas de los Receptores de Endotelina / Hemangiosarcoma Límite: Animals Idioma: En Revista: Life Sci Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Enfermedades de los Perros / Antagonistas de los Receptores de Endotelina / Hemangiosarcoma Límite: Animals Idioma: En Revista: Life Sci Año: 2016 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Países Bajos