Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action. The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells. Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC₅₀ of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells. In this study, masitinib suppressed cell proliferation concomitantly via induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells in vitro, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.

Several antidiabetic medications have been proposed as prospective treatments for cognitive impairments in type 2 diabetes patients, glibenclamide (GBC) among them. Our research aimed to evaluate the impact of GBC on hippocampal learning memory and inflammation due to enhanced neurotrophic signals induced by inhalation of sevoflurane. Rats (Sprague Dawley, both sexes) were assigned to four groups: a control (vehicle, p.o.), GBC (10 mg/kg b.w.; p.o.), low-dose sevoflurane and low-dose sevoflurane + GBC (10 mg/kg b.w.; p.o.) for 23 days. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining was performed to analyse the count of apoptotic cells and ELISA was conducted to assess the protein signals. A Western blot, a Y-maze test, and a Morris maze test were performed, and the results analysed. Blood and tissues were collected, and isolation of RNA was performed with qRT-PCR. The Morris maze test results revealed an improvement in the length of the escape latency on days 1 (P < 0.05), 2 (P < 0.01), 3, and 4 in the low-dose Sevo group. Time spent in the quadrant and crossing axis and the percentage of spontaneous alterations showed a substantial decrease in the low-dose Sevo group which received GBC at 10 mg/kg b.w. Significant increases were shown in IL-6 and TNF-α levels in the low-dose Sevo group, whereas a decrease was evident in the GBC group. Our results indicate that glibenclamide may be a novel drug to prevent sevoflurane inhalation-induced impaired learning and reduce brain-derived neurotrophic factor release, which may be a vital target for the development of potential therapies for cognitive deficits and neurodegeneration.