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. 2012 May;33(5):682-90.
doi: 10.1038/aps.2012.18. Epub 2012 Apr 16.

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Dong-bo Liu  1 , Guang-yuan Hu, Guo-xian Long, Hong Qiu, Qi Mei, Guo-qing Hu
Affiliations

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Dong-bo Liu et al. Acta Pharmacol Sin. 2012 May.

Erratum in

  • Acta Pharmacol Sin. 2013 Apr;34(4):581

Abstract

Aim: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC).

Methods: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3(Y705) (pSTAT3(Y705)), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1.

Results: Celecoxib (10-75 μmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 μmol/L) induced apoptosis and cell-cycle arrest at the G(0)/G(1) checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 μmol/L).

Conclusion: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.

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Figures

Figure 1
Figure 1
Celecoxib regulated COX-2 expression levels and inhibited cell proliferation in human nasopharyngeal carcinoma cells. (A and B) COX-2 was consistently expressed in both HNE1 and CNE1-LMP1 cell lines. Western blot analysis of the control cells and cells treated with various concentrations celecoxib (0, 10, 25, 50 or 75 μmol/L). HNE1 cells expressed higher levels of COX-2 than CNE1-LMP1 cells. COX-2 expression levels were significantly reduced in HNE1 cells but were significantly increased in the CNE1-LMP1 cells after drug treatment. (C and D) Celecoxib induced dose-dependent growth inhibition in both HNE1 and CNE1-LMP1 cells. Values displayed are the mean±SD (n=3). aP>0.05, cP<0.01 vs control; fP<0.01 CNE1-LMP1 control vs HNE1 control.
Figure 2
Figure 2
Celecoxib induced apoptosis in HNE1 and CNE1-LMP1 cells. After 48 h of incubation with drugs, flow cytometry analysis using Annexin V and propidium iodide (PI) double staining was performed on both control and celecoxib-treated cells. The population in the figure is the total number of apoptotic cells, which includes both early and late apoptotic populations. Early apoptotic cells were positive for Annexin V-FITC and negative for PI. Late apoptotic cells were positive for both Annexin V-FITC and PI. Significant apoptosis was observed in HNE1 cells (A) with 25 and 50 μmol/L of celecoxib, and in CNE1-LMP1 cells (B) with 50 and 75 μmol/L of celecoxib. The data are presented as the mean±SD (n=3). aP>0.05, bP<0.05, cP<0.01 vs control.
Figure 3
Figure 3
Celecoxib caused cell-cycle arrest in HNE1 and CNE1-LMP1 cells. Flow cytometry analysis of cells treated with DMSO (control) or celecoxib (10, 25, 50 or 75 μmol/L) for 48 h. Cells were fixed with 70% ethanol, stained with PI, and analyzed by flow cytometry. (A) Representative DNA histogram of cells after treatment with control or various concentrations of celecoxib for 48 h. Significant G0/G1 checkpoint arrest was observed in HNE1 (B) treated with 25 and 50 μmol/L of celecoxib, and this arrest was also observed in CNE1-LMP1 cells (C) treated with 25, 50 or 75 μmol/L of celecoxib. The data shown are the mean± SD from triplicate replicates and three independent experiments. aP>0.05, bP<0.05, cP<0.01 vs control.
Figure 4
Figure 4
Celecoxib inhibited STAT3 phosphorylation and down-regulated the levels of STAT3 downstream targets. HNE1 and CNE1-LMP1 cells were treated with DMSO (control) or celecoxib (10, 25, 50 or 75 μmol/L) for 48 h. Celecoxib significantly inhibited STAT3 phosphorylation in both cell lines. The pSTAT3 expression level was higher in the CNE1-LMP1 cell line than that in the HNE1 cell line (A and B). Celecoxib also down-regulated the downstream proteins of STAT3 (Survivin, Mcl-1, Bcl-2 and Cyclin D1) (C and D). The blots displayed are from a representative experiment repeated three times with similar results. aP>0.05, bP<0.05, cP<0.01 vs control; fP<0.01 CNE1-LMP1 control vs HNE1 control.
Figure 5
Figure 5
Celecoxib inhibited STAT3 phosphorylation induced by IL-6. HNE1 cells were pretreated with celecoxib for 2 h followed by 25 ng/mL of IL-6 for 30 min. Western blot analysis was performed for STAT3 phosphorylation. IL-6 promoted pSTAT3 expression, which was significantly suppressed by celecoxib at concentrations of 25 and 50 μmol/L (A and B). The blots displayed are from a representative experiment repeated three times with similar results. cP<0.01 vs control.
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References

    1. Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002;12:421–9. - PubMed
    1. Agulnik M, Epstein JB. Nasopharyngeal carcinoma: current management, future directions and dental implications. Oral Oncol. 2008;44:617–27. - PubMed
    1. Teo PM, Kwan WH, Lee WY, Leung SF, Johnson PJ. Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma. Cancer. 1996;77:2423–31. - PubMed
    1. Kim TH, Jeong YI, Jin SG, Pei J, Jung TY, Moon KS, et al. Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells. Int J Nanomed. 2011;6:2621–31. - PMC - PubMed
    1. Zhang M, Xu ZG, Shi Z, Shao D, Li O, Li W, et al. Inhibitory effect of celecoxib in lung carcinoma by regulation of cyclooxygenase-2/cytosolic phospholipase A2 and peroxisome proliferator-activated receptor gamma. Mol Cell Biochem. 2011;355:233–40. - PubMed

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