The role of celecoxib in Rad51 expression and cell survival affected by gefitinib in human non-small cell lung cancer cells

Ko, Jen-Chung; Wang, Lyu-Han; Jhan, Jhih Yuan; Ciou, Shih‐Ci; Hong, Jhao-Hao; Lin, Szu‐Ting; Lin, Yun‐Wei

doi:10.1016/j.lungcan.2008.12.008

Cited by 9 publications

(7 citation statements)

References 62 publications

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“…A first interesting observation about these genes is that many of them have been positively implicated in breast and/or lung cancer progression and resistance to therapy: AURKA [33], [34], CAV2 [35], RAB27A [36], RAD51 [37]–[39], TIMELESS [40], TIMM17A [41]. On the other hand there is evidence of a tumor-suppressing role of SPARC [42], [43].…”

Section: Resultsmentioning

confidence: 99%

Shortening of 3′UTRs Correlates with Poor Prognosis in Breast and Lung Cancer

2012

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A major part of the post-transcriptional regulation of gene expression is affected by trans-acting elements, such as microRNAs, binding the 3′ untraslated region (UTR) of their target mRNAs. Proliferating cells partly escape this type of negative regulation by expressing shorter 3′ UTRs, depleted of microRNA binding sites, compared to non-proliferating cells. Using large-scale gene expression datasets, we show that a similar phenomenon takes place in breast and lung cancer: tumors expressing shorter 3′ UTRs tend to be more aggressive and to result in shorter patient survival. Moreover, we show that a gene expression signature based only on the expression ratio of alternative 3′ UTRs is a strong predictor of survival in both tumors. Genes undergoing 3′UTR shortening in aggressive tumors of the two tissues significantly overlap, and several of them are known to be involved in tumor progression. However the pattern of 3′ UTR shortening in aggressive tumors in vivo is clearly distinct from analogous patterns involved in proliferation and transformation.

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Section: Resultsmentioning

confidence: 99%

Shortening of 3′UTRs Correlates with Poor Prognosis in Breast and Lung Cancer

2012

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“…COX-2 overexpression is seen in many malignancies including lung cancer [1]. Recently, it was shown by O’Kane et al 2010 [23] that COX-2 specific inhibitors enhance the cytotoxic effect of conventional drugs.…”

Section: Discussionmentioning

confidence: 99%

“…The prognosis of lung cancer is very poor and long-term survival is obtained in only 5-10% of the patients. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancers and is the leading cause of tumor-related death worldwide highlighting the need for more effective treatment strategies [1,2]. NSCLC are inherently resistant and are generally not responsive to initial chemotherapy [3].…”

Section: Introductionmentioning

confidence: 99%

Potentiation of in vitro and in vivoantitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells

et al. 2013

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BackgroundIn the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells.MethodsSynergistic effects of P276-00 and doxorubicin on growth inhibition was studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model.ResultsThe combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-κB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model.ConclusionThese findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-κB signaling and inhibition of Cdk-1 which is involved in cell cycle progression.

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“…Celecoxib has various roles in ERK1/2 activation in various cells. For example, in human non-small cell lung cancer cells, treatment with celecoxib alone had no effect (22). However, in human hepatic stellate cells (HSCs), celecoxib significantly attenuated ERK1/2 activation.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting ERK1/2 and SMAD2/3 phosphorylation

Fan

Zeng

et al. 2011

Mol Med Report

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Abstract. This study aimed to investigate whether celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) and SMAD2/3 phosphorylation. Celecoxib was added to NIH/3T3 fibroblasts stimulated by fibroblast growth factor-2 (FGF-2) or transforming growth factor-β1 (TGF-β1). NIH/3T3 fibroblast proliferation and viability were assessed by MTT assays; ERK1/2 expression and SMAD2/3 expression were assessed by quantitative RT-PCR and Western blot analysis. The results indicated that celecoxib suppressed cell proliferation (IC 50 FGF + group, 75±1.9 µmol/l) stimulated by FGF-2, and also inhibited cell viability (IC 50 FGF -group, 252±2.3 µmol/l) by inhibiting ERK1/2 phosphorylation but not ERK1/2 expression. In addition, celecoxib treatment led to the apoptosis of NIH/3T3 fibroblasts (IC 50 FGF -group, 35±1.4 µmol/l). Celecoxib also suppressed collagen expression (0.35-fold COL3 and 0.43-fold COL1 with 320 µmol/l celecoxib relative to the untreated group following stimulation for 3 h, p<0.01) when stimulated by TGF-β1, by inhibiting SMAD2/3 phosphorylation but not SMAD2/3 expression. Celecoxib is capable of inhibiting ERK1/2 and SMAD2/3 phosphorylation, which is responsible for NIH/3T3 fibroblast proliferation and collagen expression.

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The role of celecoxib in Rad51 expression and cell survival affected by gefitinib in human non-small cell lung cancer cells

Cited by 9 publications

References 62 publications

Shortening of 3′UTRs Correlates with Poor Prognosis in Breast and Lung Cancer

Shortening of 3′UTRs Correlates with Poor Prognosis in Breast and Lung Cancer

Potentiation of in vitro and in vivoantitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells

Celecoxib suppresses fibroblast proliferation and collagen expression by inhibiting ERK1/2 and SMAD2/3 phosphorylation

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