title: Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells.
abstract: Cyclooxygenase-2 (COX-2) has a pivotal role in the pathogenesis of the lung cancer. It is known that COX-2 negatively regulates the activity of a number of tumor suppressors, including p53. Consequently, inhibition of COX-2 signaling is anticipated to be a promising approach to stabilize p53 functionality. In this regard, we investigated the effect of COX-2 signaling blockade on p53 and COX-2expression in A549 cells. Cell viability was assessed using MTT and protein expression was measured using Western Blot assay. Results revealed that Celecoxib dose-dependently induced growth inhibition within 24 h. However, prolonged exposure to the drug up to 48 h led to increase cell viability compared to the corresponding control. Western blot analysis demonstrated that Celecoxib could augment p53 expression within 24 h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induced COX-2 expression within 48 h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48 h. These findings represent p53 as a molecular target being interconnected with COX-2 signaling axis upon Celecoxib treatment. Moreover, our data point toward the possibility that Celecoxib treatment may not be a proper therapeutic strategy in lung cancer cells owing to its potential role in the activation of oncogenes, including COX-2 and MDM2 which seemingly confers a chemoresistance circumstance to the cell. Consequently, these results underscore intensive preclinical assessment prior to applying COX-2 inhibitors in the treatment of lung tumors.
authors.affiliation: Department of Toxicology-Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Gharghabi
authors.affiliation: Department of Toxicology-Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhang
authors.initials: F
authors.lastname: Rezaei
authors.affiliation: Department of Biology, Faculty of Science, University of Mazandaran, Mazandaran, Babolsar, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Mir Mohammadrezaei
authors.affiliation: Department of Toxicology-Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Ghahremani
keywords: COX-2; Celecoxib; Crosstalk; p53