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RETRACTED ARTICLE: Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells

  • Research Article
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Tumor Biology

This article was retracted on 17 August 2015

Abstract

Cyclooxygenase-2 (COX-2) is a key limited enzyme of prostaglandin (PG) synthesis and has been demonstrated to be overexpressed in cancer. N-[2-(cyclohexyloxy)-4-nitropheny]-methane sulfonamide (NS-398) is a special inhibitor of COX-2 and may suppress PGE2 release and promote immune response mechanism of cytotoxic T lymphocytes (CTLs). We aimed to investigate the effect of NS-398 on the PGE2 release, proliferation of ovarian carcinoma cell line CAOV3, and immune cytotoxicity of CTLs. CAOV3 cells were incubated with 0, 50, and 100 μmol/L NS-398 for 24, 48, and 72 h. Cell viability was determined by trypan blue staining. PGE2 was measured using radioimmunoassay. CTLs were generated from peripheral blood mononuclear cells after stimulated by CAOV3 cells or CAOV3 cells treated with NS-398 when IL-2 existed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the cytotoxicity of CTLs. As expected, the amount, cell density, cellular volume, and growth speed of CAOV3 cells incubated with NS-398 were significantly decreased compared with control group. This difference became more obvious with an increase in the NS-398 concentration and incubation time. Similarly, PGE2 released from CAOV3 cells treated with 50 and 100 μmol/L NS-398 was significantly decreased compared with control group (P < 0.05). There was also significance in PGE2 between the two groups treated with 50 and 100 μmol/L NS-398 (P < 0.05). Compared with control group, the killing rates of CTLs to CAOV3 treated with 50 and 100 μmol/L NS-398 were significantly increased (P < 0.05). However, there is no significant difference between them. Together, our results suggest that NS-398 could be useful in prevention and therapy of ovarian carcinoma.

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Abbreviations

COX-2:

Cyclooxygenase-2

CTLs:

Cytotoxic T lymphocytes

MHC:

Major histocompatibility complex

PBMC:

Peripheral blood mononuclear cells

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

PGE2 :

Prostaglandin E2

DC:

Dendritic cells

References

  1. Bowen NJ, Walker LD, Matyunina LV, Logani S, Totten KA, Benigno BB, et al. Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells. BMC Med Genomics. 2009;2:71. doi:10.1186/1755-8794-2-71.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Wang X, Li L, Wang B, Xiang J. Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells. J Huazhong Univ Sci Technolog Med Sci. 2009;29(6):761–4. doi:10.1007/s11596-009-0618-y.

    Article  PubMed  Google Scholar 

  3. Appleby SB, Ristimaki A, Neilson K, Narko K, Hla T. Structure of the human cyclo-oxygenase-2 gene. Biochem J. 1994;302(Pt 3):723–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, et al. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res. 1995;55(17):3785–9.

    CAS  PubMed  Google Scholar 

  5. Matsubayashi H, Infante JR, Winter JM, Klein AP, Schulick R, Hruban R, et al. Tumor COX-2 expression and prognosis of patients with resectable pancreatic cancer. Cancer Biology & Ther. 2007;6(10):1569–75.

    Article  Google Scholar 

  6. Zhu J, Zhang G, Lu H. CD24, COX-2, and p53 in epithelial ovarian cancer and its clinical significance. Front in Biosci (Elite Edition). 2012;4:2745.

    Article  Google Scholar 

  7. Athanassiadou P, Grapsa D, Athanassiades P, Gonidi M, Athanassiadou AM, Tsipis A, et al. The prognostic significance of COX-2 and survivin expression in ovarian cancer. Pathol Res Pract. 2008;204(4):241–9.

    Article  PubMed  Google Scholar 

  8. Park MK, Kim MK, Kim JC, Sung YK. Pattern of apoptosis by NS398, a selective COX-2 inhibitor, in hepatocellular carcinoma cell lines. Cancer Res Treat. 2005;37(5):313–7. doi:10.4143/crt.2005.37.5.313.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Chang HC, Weng CF. Cyclooxygenase-2 level and culture conditions influence NS398-induced apoptosis and caspase activation in lung cancer cells. Oncol Rep. 2001;8(6):1321–5.

    CAS  PubMed  Google Scholar 

  10. Liu XH, Yao S, Kirschenbaum A, Levine AC. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res. 1998;58(19):4245–9.

    CAS  PubMed  Google Scholar 

  11. Youns M, Efferth T, Hoheisel JD. Transcript profiling identifies novel key players mediating the growth inhibitory effect of NS-398 on human pancreatic cancer cells. Eur J Pharmacol. 2011;650(1):170–7.

    Article  CAS  PubMed  Google Scholar 

  12. Huang M, Stolina M, Sharma S, Mao JT, Zhu L, Miller PW, et al. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res. 1998;58(6):1208–16.

    CAS  PubMed  Google Scholar 

  13. Smyth GP, Stapleton PP, Barden CB, Mestre JR, Freeman TA, Duff MD, et al. Renal cell carcinoma induces prostaglandin E 2 and T-helper type 2 cytokine production in peripheral blood mononuclear cells. Ann Surg Oncol. 2003;10(4):455–62.

    Article  PubMed  Google Scholar 

  14. Morita I, Schindler M, Regier MK, Otto JC, Hori T, DeWitt DL, et al. Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem. 1995;270(18):10902–8.

    Article  CAS  PubMed  Google Scholar 

  15. Spivak B, Lamschtein C, Talmon Y, Guy N, Mester R, Feinberg I, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin Neuropharmacol. 1999;22(2):98–101.

    Article  CAS  PubMed  Google Scholar 

  16. Inoue H, Yokoyama C, Hara S, Tone Y, Tanabe T. Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element. J Biol Chem. 1995;270(42):24965–71.

    Article  CAS  PubMed  Google Scholar 

  17. Kase S, Osaki M, Honjo S, Takeda A, Adachi K, Araki K, et al. A selective cyclooxygenase-2 inhibitor, NS398, inhibits cell growth and induces cell cycle arrest in the G2/M phase in human esophageal squamous cell carcinoma cells. J Exp Clin Cancer Res. 2004;23(2):301–7.

    CAS  PubMed  Google Scholar 

  18. Stolina M, Sharma S, Lin Y, Dohadwala M, Gardner B, Luo J, et al. Specific inhibition of cyclooxygenase 2 restores antitumor reactivity by altering the balance of IL-10 and IL-12 synthesis. J Immunol. 2000;164(1):361–70.

    Article  CAS  PubMed  Google Scholar 

  19. Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, et al. Tumor cyclooxygenase 2-dependent suppression of dendritic cell function. Clin Cancer Res. 2003;9(3):961–8.

    CAS  PubMed  Google Scholar 

  20. Sombroek CC, Stam AG, Masterson AJ, Lougheed SM, Schakel MJ, Meijer CJ, et al. Prostanoids play a major role in the primary tumor-induced inhibition of dendritic cell differentiation. J Immunol. 2002;168(9):4333–43.

    Article  CAS  PubMed  Google Scholar 

  21. Valmori D, Dutoit V, Lienard D, Rimoldi D, Pittet MJ, Champagne P, et al. Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response to the cancer testis antigen NY-ESO-1 in melanoma patients. Cancer Res. 2000;60(16):4499–506.

    CAS  PubMed  Google Scholar 

  22. Nizamutdinova IT, Lee JH, Seo HG, Chang KC, Kim HJ. NS398 protects cells from sodium nitroprusside-mediated cytotoxicity through enhancing HO-1 induction independent of COX-2 inhibition. Arch Pharm Res. 2009;32(1):99–107. doi:10.1007/s12272-009-1123-3.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work is supported by the Natural Science Foundation of China (Grant Number: 30973189).

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Correspondence to Min Wang.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s13277-015-3694-6.

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

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Wang, X., Liang, Y., Wang, J. et al. RETRACTED ARTICLE: Effect of NS-398, a cyclooxygenase-2 selective inhibitor, on the cytotoxicity of cytotoxic T lymphocytes to ovarian carcinoma cells. Tumor Biol. 34, 1517–1522 (2013). https://doi.org/10.1007/s13277-013-0677-3

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  • DOI: https://doi.org/10.1007/s13277-013-0677-3

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