Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines
Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines
Data
2009
Autores
Duarte, Mariana Lemos
Moraes, Emanuela de
Pontes, Elizangela
Schluckebier, Luciene
Moraes, Joyce Luana de
Hainaut, Pierre
Ferreira, Carlos Gil
Journal Title
Journal ISSN
Volume Title
Publisher
Cancer Letters
Resumo
Non-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.
Description
Palavras-chave
Cyclooxygenase-2, p53, Chemotherapy, Lung cancer
Citação
Duarte 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