Work

Modulation of the endocannabinoid system reduces inflammatory signalling in canine mammary carcinoma cells

Year: 2026

Type: article

Abstract: Background Canine mammary carcinoma (CMC) is characterised by a chronic inflammatory microenvironment resembling human breast cancer; however, the upstream regulatory mechanisms driving this phenotype remain unclear. The endocannabinoid system (ECS) has emerged as a potential modulator of inflammation and tumour biology. This study investigated the role of the ECS in CMC and evaluated the anti‐inflammatory effects of cannabidiol (CBD). Methods Primary cell cultures were established from surgically excised CMC tissues, with matched normal mammary epithelium used as controls. Basal mRNA expression of ECS‐related receptors (CB1, CB2, transient receptor potential vanilloid 1 [TRPV1], G‐protein‐coupled receptor 55 [GPR55] and peroxisome proliferator‐activated receptor alpha [PPAR‐α]) and inflammatory mediators (COX‐1, COX‐2, interleukin [IL]‐4, IL‐6, IL‐33, IL‐17A, tumour necrosis factor‐alpha [TNF‐α] and LCN2) was assessed by reverse transcription quantitative polymerase chain reaction. Cytokine secretion (IL‐6, IL‐8, TNF‐α and IL‐17A) was quantified by enzyme‐linked immunosorbent assay. Cell viability assays were performed to determine the 24‐h IC 50 of CBD (32 µM), and sub‐cytotoxic concentrations (3, 10 and 20 µM) were subsequently applied for 24 h. Results Canine mammary carcinoma‐derived cells exhibited significant overexpression of ECS receptors (CB1, CB2, TRPV1, GPR55 and PPAR‐α) compared to normal controls. These cells also showed increased secretion of pro‐inflammatory cytokines, including IL‐6, IL‐8, TNF‐α and IL‐17A. Treatment with CBD at 10–20 µM significantly downregulated key inflammatory genes, particularly COX‐2, IL‐6 and TNF‐α, and reduced corresponding cytokine release without compromising cell viability. Conclusion The ECS is upregulated in CMC and appears to contribute to the inflammatory tumour microenvironment. Cannabidiol effectively attenuates this inflammatory phenotype at sub‐cytotoxic concentrations, supporting its potential as a therapeutic agent in CMC.

Source: Veterinary Record Open

DOI: 10.1002/vro2.70034