Celecoxib treatment alters p53 and mdm2 expression via COX-2 crosstalk in A549 cells

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. © 2016 by school of pharmacy.