Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines

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dc.contributor.authorDuarte, Mariana Lemos
dc.contributor.authorMoraes, Emanuela de
dc.contributor.authorPontes, Elizangela
dc.contributor.authorSchluckebier, Luciene
dc.contributor.authorMoraes, Joyce Luana de
dc.contributor.authorHainaut, Pierre
dc.contributor.authorFerreira, Carlos Gil
dc.date.accessioned2024-10-08T17:30:43Z
dc.date.available2024-10-08T17:30:43Z
dc.date.issued2009
dc.description.abstractNon-small cell lung Cancer (NSCLC) is extremely resistant to chemotherapeutic agents, such as cisplatin. High expression of the inflammatory enzyme Cyclooxygenase-2 (COX- 2) has been shown to inhibit chemotherapy-induced apoptosis, but little is known about COX-2 regulation upon drug treatment. Recent data indicate the tumor suppressor protein p53 as an important regulator of COX-2. Therefore, TP53 status could change tumor sensi- tivity to chemotherapy through induction of the anti-apoptotic protein COX-2. The main objective of this work was to analyze the effect of chemotherapy on the expression of COX-2, according to TP53 status. We report herein that lung cancer cell lines expressing wild-type p53, when exposed to cisplatin treatment, induced COX-2 (mRNA and protein), with concurrent synthesis of prostaglandins (PGE2). In contrast, COX-2 expression was not changed after cisplatin treatment of cells containing an inactive form of p53. Further, after silencing of wild-type p53 expressed in A549 cells by RNA interference, cisplatin was no longer able to induce COX-2 expression. Therefore, we suggest that induction of COX-2 by cisplatin in NSCLC cell lines is dependent on p53. For paclitaxel treatment, an increase in COX-2 mRNA expression was observed in H460 and A549 (wild-type p53 cell lines). Moreover, paclitaxel treatment increased COX-2 expression in ACC-LC-319 cell lines (p53 null), showing a p53-independent effect. These data may have therapeutic implica- tions in the selection of patients and strategy for future COX-2 inhibition trials.
dc.identifier.citationDuarte ML, de Moraes E, Pontes E, Schluckebier L, de Moraes JL, Hainaut P, Ferreira CG. Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines. Cancer Lett. 2009 Jun 28;279(1):57-64. doi: 10.1016/j.canlet.2009.01.021
dc.identifier.otherDOI: 10.1016/j.canlet.2009.01.021
dc.identifier.urihttps://dspace.inc.saude.gov.br/handle/123456789/478
dc.language.isoen
dc.publisherCancer Letters
dc.subjectCyclooxygenase-2en
dc.subjectp53en
dc.subjectChemotherapyen
dc.subjectLung canceren
dc.titleRole of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines
dc.typeArticle
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