Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells

Gharghabi, Mehdi; Rezaei, Farhang; Mir Mohammadrezaei, Fereshteh; Ghahremani, Mohammad Hossein

doi:10.22037/ijpr.2016.1849

Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells

Document Type : Research article

Authors

¹ Department of Toxicology-Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

² Department of Biology, Faculty of Science, University of Mazandaran, Mazandaran, Babolsar, Iran

³ Tehran University of Medical Sciences

10.22037/ijpr.2016.1849

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-2 expression 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 24h. However, prolonged exposure to the drug up to 48h led to increase cell viability compared to the corresponding control. Western blot analyses demonstrated that Celecoxib could augment p53 expression within 24h, independently of COX-2 inhibition. In contrast, Celecoxib treatment not only returned p53 to the control level, but also strikingly induce COX-2 expression within 48h. Of further relevance, Celecoxib exposure could significantly result in MDM2 elevation at 48h. 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.

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