論文

基本情報

氏名 小林 宏祐
氏名(カナ) コバヤシ コウスケ
氏名(英語) Kobayashi Kosuke
所属 獣医学部 獣医学科
職名 講師
researchmap研究者コード R000002187
researchmap機関 岡山理科大学

単著・共著の別

単著

著者

Kosuke Kobayashi, Kohei Murakami, Kenji Baba

概要

Canine haemangiosarcoma (HSA) is a highly aggressive cancer often associated with coagulation abnormalities. Statins, inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) clinically prescribed for hypercholesterolemia, are also believed to possess antitumour and anticoagulant properties by inhibiting downstream Akt activation. Akt phosphorylation is involved in the mechanism of the antitumour and tissue factor (TF)-lowering effects of statins. In the present study, we aimed to investigate whether statins could inhibit cell viability while concurrently inducing anticoagulant properties by regulating the expression of TFs in canine HSA cells. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), we initially exclusively detected HMGCR mRNA expression in canine HSA tissues and cell lines but not in normal cephalic vein and spleen tissues. Moreover, treatment with lipophilic statins, including atorvastatin, fluvastatin, and simvastatin, inhibited cell viability in a concentration-dependent manner and decreased TF expression both at the mRNA and protein levels, as evidenced by cell viability assays, RT-qPCR, and immunoblotting, respectively. Further investigation using cell viability assays and flow cytometry revealed that simvastatin decreased Akt phosphorylation, and MK-2206, a specific Akt inhibitor, mirrored the effect of simvastatin on cell viability and cell cycle arrest. However, MK-2206 exhibited different effects on TF expression depending on the cell type, indicating that Akt phosphorylation may not consistently regulate TF expression. Overall, this study provides insights into the potential therapeutic use of statins in targeting tumour growth and coagulation abnormalities in canine HSA. Further research is warranted to fully elucidate the underlying mechanisms and clinical applications of statins in canine HSA treatment.

発表雑誌等の名称

Veterinary Comparative Oncology

出版者

22

4

開始ページ

581

終了ページ

591

発行又は発表の年月

2024/12

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

ISSN

ID:DOI

10.1111/vco.13012

ID:NAID(CiNiiのID)

ID:PMID

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID