title: Change in nicotine-induced VEGF, PGE2 AND COX-2 expression following COX inhibition in human oral squamous cancer.
abstract: Cigarette smoke has been documented to be related to the development of cancer. However, the exact mechanism for the carcinogenic action of cigarette smoke is still unknown. Nicotine is recognized to be the major compound in cigarette smoke and has been suggested to play a role in oral cancer via a cyclooxygenase (COX)/ prostaglandin-dependent pathway. This study was designed to evaluate the action of nicotine in the oral cancer cell and to further examine whether COX-2 is responsible for expression of tumor-associated angiogenic vascular endothelial growth factor (VEGF) in vitro. Viability of human oral squamous cancer cells (BHY) was measured using MTT assay. Protein expression was determined by Western blot and immunoassay kits. We found that exposure of BHY cells to nicotine (200 µg/mL for 6 hours) resulted in 2.9-fold induction of COX-2 expression as well as a 4-fold increase in VEGF levels compared with a control group. Pretreatment with celecoxib inhibited nicotine-induced change in the expression of VEGF and COX-2. The results suggest that stimulation of COX-2 and VEGF expression can contribute as important factors in the tumorigenic action of nicotine in oral cancer progression. This effect can be blocked by celecoxib, suggesting an interaction of nicotine and COX-2 pathways.
authors: Departments of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran. Salimimona@pasteur.ac.ir
authors: Mona
authors: M
authors: Salimi
authors: Masoumeh
authors: M
authors: Esfahani
authors: Narcis
authors: N
authors: Habibzadeh
authors: Hamid Reza
authors: HR
authors: Aslani
authors: Amir
authors: A
authors: Amanzadeh
authors: Mehrangiz
authors: M
authors: Esfandiary
authors: Bita
authors: B
authors: Sedaghati
authors: Sepideh Arbabi
authors: SA
authors: Bidgoli
authors: Mohammad Hossein
authors: MH
authors: Ghahremani
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D000068579:Celecoxib; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D009538:Nicotine / Q000633:toxicity*; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009538:Nicotine; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D000068579:Celecoxib; D015232:Dinoprostone