title: The role of COX-2 inhibitors in lung cancer.
abstract: BACKGROUND
  Human lung cancer is a major cause of death worldwide with few known effective therapeutic modalities. The isoenzyme cyclooxygenase 2 (COX-2) is an inducible inflammatory enzyme with increased activity evidenced in lung carcinoma. The objective was to determine the effect of a selective COX-2 inhibitor on proliferation and apoptosis rates in the Lewis lung (3LL) tumor cell line in vitro.
  
  
  METHODS
  First, 1 x 10(4) 3LL cells were plated in a 96-well plate. Cells were incubated for 24 hours with either a control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete Dulbecco's Modified Eagle's Medium culture medium. Cell proliferation was measured using BrdU enzyme-linked immunosorbent assay. Next, 1 x 10(6) 3LL cells were similarly treated. Cells were permeabilized, immunostained with propidium iodide and apoptotic rates were measured using flow cytometry. Then, 5 x 10(4) cells were plated on a 24-well plate. Cells were incubated for 24 hours with either control or increasing doses of rofecoxib (0.1 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.5 mmol/L) in complete culture medium. Supernatant was collected and lactate dehydrogenase was measured for cell necrosis using a cytotoxicity detection kit.
  
  
  RESULTS
  The selective COX-2 inhibitor rofecoxib resulted in a dose-dependent increase in apoptosis and dose and time-dependent growth inhibition in cell proliferation. However, rofecoxib did not cause cell necrosis.
  
  
  CONCLUSIONS
  There was a significant decrease in proliferation and increase in apoptosis of 3LL tumor cells when treated with the highly selective COX-2 inhibitor rofecoxib. COX-2 inhibitors may have a potential role to play in the treatment of lung carcinoma.
authors.affiliation: Department of Cardiothoracic Surgery, Cork University Hospital, Wilton, Republic of Ireland.
authors.forename: Syed Suhail Ahmed
authors.initials: SS
authors.lastname: Qadri
authors.forename: Jiag Huai
authors.initials: JH
authors.lastname: Wang
authors.forename: Karen Christina
authors.initials: KC
authors.lastname: Redmond
authors.forename: Aonghus F
authors.initials: AF
authors.lastname: O' Donnell
authors.forename: Thomas
authors.initials: T
authors.lastname: Aherne
authors.forename: Henry Paul
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D013450:Sulfones; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
chemical_list: D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib