Role of cytokines in experimentally induced lung cancer and chemoprevention by COX-2 selective inhibitor, etoricoxib
Menée sur un modèle murin de cancer du poumon induit par le benzo anthracène (diméthyl), cette étude analyse l'effet chimiopréventif de l'étoricoxib, un anti-inflammatoire non stéroïdien inhibiteur de la cyclo-oxygénase 2, sur les niveaux d'expression des cytokines pro- et anti-inflammatoires
This study explored the role of pro- and anti-inflammatory cytokines in dimethyl benz(a)anthracene (DMBA)-induced lung cancer and its subsequent correction with a COX-2 inhibitory NSAID, etoricoxib. A single dose of DMBA (20 mg/kg body weight) in 0.9 % NaCl administered intratracheally was used to induce tumors in the rat lungs in 20 weeks. The study of pro-inflammatory cytokines like IL-1beta, TNF-alpha, and IFN-gamma revealed their upregulation by DMBA administration and restoration of their levels toward normal by the treatment with etoricoxib, while the anti-inflammatory cytokine IL-2 was found to be down-regulated with carcinogen administration and corrected with etoricoxib treatment. Apoptosis was studied by mitochondrial Bcl-2/Bax ratio and staining with fluorescent dyes acridine orange/ethidium bromide. The results showed a decreased apoptotic level with DMBA which was corrected with etoricoxib. Also, mitochondrial membrane potential was studied using JC-1 and rhodamine-123, which are membrane permeant fluorescent dyes, and generate information about cells at lower and higher mitochondrial membrane potential (Psi(M)). The results showed the presence of maximum number of cells with higher Psi(M) in the DMBA group and their number was considerably lowered in the other three groups.