Academic Thesis

Basic information

Name Kobayashi Kosuke
Belonging department
Occupation name
researchmap researcher code R000002187
researchmap agency Okayama University of Science

Bibliography Type

Sole Author

Author

Kosuke Kobayashi, Kohei Murakami, Kenji Baba

Summary

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.

Magazine(name)

Veterinary Comparative Oncology

Publisher

Volume

22

Number Of Pages

4

StartingPage

581

EndingPage

591

Date of Issue

2024/12

Referee

Exist

Invited

Not exist

Language

English

Thesis Type

Research papers (academic journals)

ISSN

DOI

10.1111/vco.13012

NAID

PMID

J-GLOBAL ID

arXiv ID

ORCID Put Code

DBLP ID