Role of neurokinin‐1 receptor during the transition of inflammation to dysplasia in a colitis‐associated colon cancer model

Long‐standing colitis markedly increases the risk of developing colorectal cancer. Neurokinin‐1 receptors (NK‐1R) have been shown to be involved in chronic colonic inflammation but their role in the transition to dysplasia is unclear. Aim To investigate the role of NK‐1R in a novel model of colitis‐associated dysplasia. Methods Sprague Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol ic), followed six weeks later by reactivation with TNBS (5 mg/kg iv) for three days. To induce colitis‐associated dysplasia the rats then received TNBS (iv) twice a week for ten weeks. One group received the NK‐1R antagonist SR140333 (1 mg/kg ip) twice a week for ten weeks; the rest received vehicle. After sacrifice the colons were removed and analyzed for total macroscopic damage, histological analysis, and real‐time RT‐PCR. Results Pathological analysis revealed a decreased incidence of dysplasia in animals treated with the NK‐1R antagonist compared with the vehicle treated group. Animals receiving SR140333 had significantly less macroscopic and microscopic damage, and a down‐regulation of mRNA levels for EGFR and NK‐1R, which correlated with the pathology. Conclusion Our results suggest that a selective NK‐1R antagonist can delay the development of damage and dysplasia in a novel model of colitis‐associated dysplasia, offering its potential therapeutic use. 1U56 CA126379 ‐01 & 1F31 GM078951 .