Effects of Lipophilic Statins on Cell Viability and Tissue Factor Expression in Canine Haemangiosarcoma Cells.

Autor: Kobayashi K; Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Japan., Murakami K; Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Japan., Baba K; Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
Jazyk: angličtina
Zdroj: Veterinary and comparative oncology [Vet Comp Oncol] 2024 Dec; Vol. 22 (4), pp. 581-591. Date of Electronic Publication: 2024 Sep 25.
DOI: 10.1111/vco.13012
Abstrakt: 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.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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