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

Content Provider	Europe PMC
Author	Gharghabi, Mehdi Rezaei, Farhang Mir mohammadrezaei, Fereshteh Ghahremani, Mohammad Hossein
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.
ISSN	17350328
Journal	Iranian Journal of Pharmaceutical Research : IJPR
Volume Number	15
PubMed Central reference number	PMC5018276
Issue Number	2
PubMed reference number	27642319
e-ISSN	17266890
Language	English
Publisher	Shaheed Beheshti University of Medical Sciences
Publisher Date	2016-01-01
Publisher Place	Tehran, Iran
Access Restriction	Open
Rights License	© 2016 by School of PharmacyShaheed Beheshti University of Medical Sciences and Health Services
Subject Keyword	p53 COX-2 Crosstalk Celecoxib
Content Type	Text
Resource Type	Article
Subject	Pharmacology, Toxicology and Pharmaceutics Pharmacology (medical)