Therapeutic potential of endothelin inhibitors in canine hemangiosarcoma

详细信息    查看全文

• 作者：Shinya Fukumoto^a ; Kaname Saida^b ; Hiroki Sakai^c ; Hiroshi Ueno^d ; Hidetomo Iwano^e ; Tsuyoshi Uchide^f ; ^{uchide@cc.tuat.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dog ; Endothelin-1 ; Hemangiosarcoma ; Tumor
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：159
• 期：Complete
• 页码：55-60
• 全文大小：539 K

文摘

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.