title: Role of cytokines in experimentally induced lung cancer and chemoprevention by COX-2 selective inhibitor, etoricoxib.
abstract: 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-1β, TNF-α, and IFN-γ 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 (∆Ψ(M)). The results showed the presence of maximum number of cells with higher ∆Ψ(M) in the DMBA group and their number was considerably lowered in the other three groups.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors.forename: Neeti
authors.initials: N
authors.lastname: Nadda
authors.forename: Shruti
authors.initials: S
authors.lastname: Setia
authors.forename: Vivek
authors.initials: V
authors.lastname: Vaish
authors.forename: Sankar Nath
authors.initials: SN
authors.lastname: Sanyal
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D018890:Chemoprevention; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000077613:Etoricoxib; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; C494828:Bax protein, rat; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D013450:Sulfones; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; D000077613:Etoricoxib