Therapeutic trial of fluvastatin in a cell line xenograft model of canine mammary gland cancer.
Humans
Animals
Dogs
Mice
Female
Fluvastatin
/ therapeutic use
Transcription Factors
/ metabolism
Heterografts
Mammary Glands, Human
/ metabolism
Cell Line, Tumor
Dog Diseases
/ drug therapy
Breast Neoplasms
/ veterinary
Mammary Neoplasms, Animal
/ drug therapy
Lung Neoplasms
/ drug therapy
Necrosis
/ veterinary
Doxorubicin
RNA, Messenger
Rodent Diseases
CMT cell line
YAP and TAZ
canine mammary tumours
fluvastatin
murine xenograft
Journal
Veterinary and comparative oncology
ISSN: 1476-5829
Titre abrégé: Vet Comp Oncol
Pays: England
ID NLM: 101185242
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
05
07
2023
received:
12
12
2022
accepted:
06
07
2023
medline:
17
11
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
ppublish
Résumé
The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki-67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry-based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.
Substances chimiques
Fluvastatin
4L066368AS
Transcription Factors
0
Doxorubicin
80168379AG
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
634-645Subventions
Organisme : Fonds du centenaire, Faculté de médecine vétérinaire, Université de Montréal
Organisme : Canadian Foundation for Innovation
Organisme : Fonds de Recherche du Québec
Organisme : Government of Quebec
ID : 36706
Organisme : Canada Research Chair in Metrology of Bioactive Molecule and Target Discovery
ID : CRC-2021-00160
Informations de copyright
© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.
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