Vet Med - Czech, 2026, 71(6):230-244 | DOI: 10.17221/48/2025-VETMED

Impact of histological and molecular subtype on the potential therapeutic effect of buparlisib in canine mammary gland tumoursOriginal Paper

A Baykal Ugur ORCID...¹, G Guney Eskiler ORCID...², O Turna ORCID...¹

¹ Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkiye

² Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkiye

This study aims to evaluate the response of primary cells to buparlisib, a PI3K inhibitor, at varying concentrations and exposure durations across different histological and molecular subtypes of CMGTs, and to assess PI3K/Akt/mTOR pathway activity by measuring Akt and mTOR expression. Three carcinomas (C), three sarcomas (S), and two carcinosarcomas (CS) tumours were collected from the dogs. The primary cells were produced from tissues and treated with buparlisib at different doses. Subsequently, the WST-1 assay, Annexin V, and AO/PI staining were performed sequentially to evaluate the effects of buparlisib. PI3K/Akt/mTOR signalling pathway inhibition was revealed at the gene level in C, S, and CS cells following 5 µM buparlisib treatment by RT-PCR analysis. Our results demonstrated that C1 and C2 (basal-like) cells were more sensitive than C3, CS1, and CS2 cells (luminal A) upon buparlisib treatment. Liposarcoma S2 cells responded more to buparlisib than undifferentiated S cells (S1 and S3). Buparlisib also induced apoptosis and inhibited Akt and mTOR mRNA levels in C2, C3, S2 and S3 cells (P < 0.05). A higher rate of apoptotic cell death was observed in the C histological subtype and basal-like cells, with 62.9 ± 0.8% apoptosis in C1 and 79.1 ± 0.3% in C2. The efficacy of buparlisib was more pronounced in C2 basal-like CMGT cells and liposarcoma S2 cells with the downregulation of Akt and mTOR mRNA levels (P < 0.001). Therefore, PI3K inhibitors could be used to treat CMGT, particularly the basal-like molecular subtype.

Keywords: apoptosis; dog; molecular classification; PI3K, Akt, mTOR signalling pathway; tyrosin kinase inhibitors

Received: July 1, 2025; Revised: February 17, 2026; Accepted: February 24, 2026; Published: June 29, 2026  Show citation