Role of cytokines in experimentally induced lung cancer and chemoprevention by COX-2 selective inhibitor, etoricoxib

Mol Cell Biochem. 2013 Jan;372(1-2):101-12. doi: 10.1007/s11010-012-1451-3. Epub 2012 Sep 19.

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.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Chemoprevention
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytokines / physiology*
  • Etoricoxib
  • Female
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Lung / drug effects
  • Lung / pathology
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / prevention & control*
  • Membrane Potential, Mitochondrial / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfones / pharmacology*
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticarcinogenic Agents
  • Bax protein, rat
  • Cyclooxygenase 2 Inhibitors
  • Cytokines
  • Inflammation Mediators
  • Proto-Oncogene Proteins c-bcl-2
  • Pyridines
  • Sulfones
  • bcl-2-Associated X Protein
  • 9,10-Dimethyl-1,2-benzanthracene
  • Etoricoxib