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

Duarte, Mariana Lemos; Moraes, Elaine Lazzaroni; Pontes, Elizangela; Schluckebier, Luciene; Moraes, Joyce; Hainaut, Pierre; Ferreira, Carlos Gil

doi:10.1016/j.canlet.2009.01.021

Cited by 21 publications

(18 citation statements)

References 26 publications

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“…Ineffective response and high resistance of lung cancer cells to chemotherapy result from induction of COX-2 and PGE2 (28,41). We found that galectin-1 knockdown may block the cisplatin-induced COX-2 and PGE2 expression and increase the response of cancer cells to cisplatin treatment ( Fig.…”

Section: Discussionmentioning

confidence: 71%

Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Chung

Tang

Sun

et al. 2012

Clinical Cancer Research

134

112

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Purpose: This study is aimed at investigating the role and novel molecular mechanisms of galectin-1 in lung cancer progression.Experimental Design: The role of galectin-1 in lung cancer progression was evaluated both in vitro and in vivo by short hairpin RNA (shRNA)-mediated knockdown of galectin-1 in lung adenocarcinoma cell lines. To explore novel molecular mechanisms underlying galectin-1-mediated tumor progression, we analyzed gene expression profiles and signaling pathways using reverse transcription PCR and Western blotting. A tissue microarray containing samples from patients with lung cancer was used to examine the expression of galectin-1 in lung cancer.Results: We found overexpression of galectin-1 in non-small cell lung cancer (NSCLC) cell lines. Suppression of endogenous galectin-1 in lung adenocarcinoma resulted in reduction of the cell migration, invasion, and anchorage-independent growth in vitro and tumor growth in mice. In particular, COX-2 was downregulated in galectin-1-knockdown cells. The decreased tumor invasion and anchorage-independent growth abilities were rescued after reexpression of COX-2 in galectin-1-knockdown cells. Furthermore, we found that TGF-b1 promoted COX-2 expression through galectin-1 interaction with Ras and subsequent activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and NF-kB pathway. Galectin-1 knockdown sensitized lung cancer cells to platinum-based chemotherapy (cisplatin). In addition, galectin-1 and COX-2 expression was correlated with the progression of lung adenocarcinoma, and high clinical relevance of both proteins was evidenced (n ¼ 47).Conclusions: p38 MAPK, ERK, and COX-2 activation are novel mediators for the galectin-1-promoted tumor progression and chemoresistance in lung cancer. Galectin-1 may be an innovative target for combined modality therapy for lung cancer. Clin Cancer Res; 18(15); 4037-47. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 71%

Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Chung

Tang

Sun

et al. 2012

Clinical Cancer Research

134

112

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“…Recently, Duarte et al (2009) presented evidence that induction of COX-2 by paclitaxel in A549 cells was independent or dependent on the expression of p53. These results indicated that an increase of COX-2 is not associated with induction of apoptosis in our investigation and it is each regulated independently.…”

Section: Discussionmentioning

confidence: 99%

Gallotannin regulates apoptosis and COX-2 expression via Akt and p38kinase pathway in human lung cancer cell line, A549

Gweon

Chung

et al. 2012

Animal Cells and Systems

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Gallotannin (GT) is derived from plant poly phenol and is associated with biological actions in a wide range of cells. In this study, we evaluated the effect of GT on apoptosis and cyclooxygenase-2 (COX-2) expression and attempted to shed light on the mechanism of action in A549 human lung carcinoma cells. We found that GT dramatically induced apoptosis as demonstrated by expression of p53 and active caspase-3 via western blot analysis and fragmented DNA as detected by DNA fragmentation and DAPI staining. We also observed that GT significantly causes COX-2 expression in a dose-dependent manner determined by western blot analysis. Phosphorylation of Akt and p38 was considerably increased by GT in A549 human lung carcinoma cells. Inhibition of Akt and p38kinase with LY294002 or SB203580 suppressed GT-induced apoptosis and COX-2 expression. Furthermore, we have shown that prevention of COX-2 with NS398 or indomethacin does not any effects on apoptosis induced by GT. Taken together, our present results suggest that GT regulates apoptosis and COX-2 expression through Akt and p38kinase pathway in A549, human lung carcinoma cells.

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“…The MDM2-p53 pathway has been recognized as an ideal therapeutic target for cancer treatment [55]. MCT-1 promotes angiogenesis that might be achieved by deregulating p53 downstream targets, such as, TSP1, VEGF, and COX-2 [56-58]; by inhibiting the MDM2-HIF-1α interaction [59,60]; or by enhancing the Twist-HIF-1α regulation [53]. Understanding of the crosstalk between MCT-1 and p53 in depth may facilitate the development of a new promising cancer therapeutic strategy that improves the therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

Kasiappan

Shih

et al. 2010

Mol Cancer

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BackgroundMCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes.ResultsMCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1) are constantly stimulated by MCT-1 oncoprotein.ConclusionsThe oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.

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

Cited by 21 publications

References 26 publications

Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Gallotannin regulates apoptosis and COX-2 expression via Akt and p38kinase pathway in human lung cancer cell line, A549

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

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