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Information Journal Paper

Title

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

Pages

  483-489

Keywords

p53 

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.

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  • Cite

    APA: Copy

    Gharghabi, Mehdi, Rezaei, Farhang, Mir mohammadrezaei, Fereshteh, & GHAHREMANI, MOHAMMAD HOSEIN. (2016). Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), 15(2), 483-489. SID. https://sid.ir/paper/288633/en

    Vancouver: Copy

    Gharghabi Mehdi, Rezaei Farhang, Mir mohammadrezaei Fereshteh, GHAHREMANI MOHAMMAD HOSEIN. Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR)[Internet]. 2016;15(2):483-489. Available from: https://sid.ir/paper/288633/en

    IEEE: Copy

    Mehdi Gharghabi, Farhang Rezaei, Fereshteh Mir mohammadrezaei, and MOHAMMAD HOSEIN GHAHREMANI, “Celecoxib Treatment Alters p53 and MDM2 Expression via COX-2 Crosstalk in A549 Cells,” IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH (IJPR), vol. 15, no. 2, pp. 483–489, 2016, [Online]. Available: https://sid.ir/paper/288633/en

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