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The Cyclooxygenase-2 Inhibitor Nimesulide, a Nonsteroidal Analgesic, Decreases the Effect of Radiation Therapy in Head-and-Neck Cancer Cells

Der Cyclooxygenase-2-Inhibitor Nimesulid, ein nichtsteroidales Analgetikum, vermindert den Effekt von Strahlentherapie in Kopf- und Halstumorzellen

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Background:

No data are available on the effects of the cyclooxygenase-2 (COX-2) inhibitor nimesulide in combination with irradiation on the survival of head-and-neck carcinoma cells.

Material and Methods:

Two head-and-neck carcinoma cell lines (SCC9 and SCC25) were treated with nimesulide (50–600 μM) and irradiated concomitantly or sequentially. Early effects on cell survival were investigated by counting cell numbers, long-term effects by colony-forming assays. Cell-cycle effects were analyzed 24–72 h after treatment with nimesulide by flow cytometry.

Results:

Unexpectedly, nimesulide solely inhibited cell proliferation without affecting colony-forming ability. In addition, no evidence for a radiosensitizing effect of nimesulide in short-term assays was seen. Nimesulide alone had no effect on clonogenic survival alone or in combination with radiation.

Conclusion:

Nimesulide differentially affects cell proliferation and clonogenic survival and may decrease the efficacy of radiotherapy. Short-term assays to assess tumor growth may not correctly predict the clinically relevant long-term effect of COX-2 inhibitors.

Hintergrund:

Bis dato gibt es keine Untersuchungen bezüglich der Anwendung des Cyclooxygenase-2-Hemmers Nimesulid in Kombination mit Bestrahlung auf Zellen des Kopf-Hals-Bereichs.

Material und Methodik:

Zwei Zelllinien des Kopf-Hals-Bereichs (SCC9 und SCC25) wurden mit Nimesulid (50–600 μM) behandelt und zeitversetzt oder konkomitant bestrahlt. Die Kurzzeiteffekte auf das Überleben der Zellen wurden mittels Zellzählung untersucht, Langzeiteffekte via Koloniebildungsassays. Mittels Durchflusszytometrie wurden die Auswirkungen auf den Zellzyklus 24, 48 und 72 h nach Behandlung evaluiert.

Ergebnisse:

Nimesulid allein war in der Lage, die Zellproliferation kurzfristig zu hemmen (Abbildungen 1, 2 und 4), allerdings ohne nachhaltigen Effekt auf die Koloniebildungsfähigkeit (Abbildungen 3 und 5). Darüber hinaus konnte weder in den Kurzzeit- (Abbildungen 2 und 4) noch in den Langzeituntersuchungen (Abbildungen 3 und 5) ein die Strahlentherapie unterstützender Effekt nachgewiesen werden.

Schlussfolgerung:

Nimesulid hat unterschiedliche Effekte auf die Zellproliferation und die Koloniebildungsfähigkeit und könnte die Effizienz der Strahlentherapie schwächen. Weiters bestätigt sich, dass aus Kurzzeitanalysen des Tumorwachstums nicht automatisch auf das klinisch relevante Langzeitergebnis geschlossen werden darf.

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References

  1. Aapro MS, Alberts DS, Salmon SE. Interactions of human leukocyte interferon with vinca alkaloids and other chemotherapeutic agents against human tumors in clonogenic assay. Cancer Chemother Pharmacol 1983;10:161–6.

    Article  PubMed  CAS  Google Scholar 

  2. Bartkowiak D, Hipp PR, Mendonca MS, et al. A radioprotective effect of imatinib (Gleevec) in human squamous carcinoma cells. Strahlenther Onkol 2007;183:432–9.

    Article  PubMed  Google Scholar 

  3. Boolbol SK, Dannenberg AJ, Chadburn A, et al. Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res 1996;56:2556–60.

    PubMed  CAS  Google Scholar 

  4. Chan G, Boyle JO, Yang EK, et al. Cyclooxygenase-2 expression is upregulated in squamous cell carcinoma of the head and neck. Cancer Res 1999;59:991–4.

    PubMed  CAS  Google Scholar 

  5. Choy H, Milas L. Enhancing radiotherapy with cyclooxygenase-2 enzyme inhibitors: a rational advance? J Natl Cancer Inst 2003;95:1440–52.

    PubMed  CAS  Google Scholar 

  6. Dannenberg AJ, Altorki NK, Boyle JO, et al. Inhibition of cyclooxygenase-2: an approach to preventing cancer of the upper aerodigestive tract. Ann N Y Acad Sci 2001;952:109–15.

    Article  PubMed  CAS  Google Scholar 

  7. Dannenberg AJ, Altorki NK, Boyle JO, et al. Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2001;2:544–51.

    Article  PubMed  CAS  Google Scholar 

  8. Day GL, Blot WJ. Second primary tumors in patients with oral cancer. Cancer 1992;70:14–9.

    Article  PubMed  CAS  Google Scholar 

  9. DuBois RN, Shao J, Tsujii M, et al. G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2. Cancer Res 1996;56:733–7.

    PubMed  CAS  Google Scholar 

  10. Dunst J, Sauer R. Simultaneous radiochemotherapy. Strahlenther Onkol 1993;169:205–12.

    PubMed  CAS  Google Scholar 

  11. Eibl G, Reber HA, Wente MN, et al. The selective cyclooxygenase-2 inhibitor nimesulide induces apoptosis in pancreatic cancer cells independent of COX-2. Pancreas 2003;26:33–41.

    Article  PubMed  CAS  Google Scholar 

  12. Eich HT, Löschcke M, Scheer M, et al. Neoadjuvant radiochemotherapy and radical resection for advanced squamous cell carcinoma of the oral cavity. Outcome of 134 patients. Strahlenther Onkol 2008;184:23–9.

    Article  PubMed  Google Scholar 

  13. Elder DJ, Halton DE, Hague A, et al. Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2(COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. Clin Cancer Res 1997;3:1679–83.

    PubMed  CAS  Google Scholar 

  14. Erovic BM, Pelzmann M, Turhani D, et al. Differential expression pattern of cyclooxygenase-1 and -2 in head and neck squamous cell carcinoma. Acta Otolaryngol 2003;23:950–3.

    Article  CAS  Google Scholar 

  15. Furuta Y, Hall ER, Sanduja S, et al. Prostaglandin production by murine tumors as a predictor for therapeutic response to indomethacin. Cancer Res 1988;48:3002–7.

    PubMed  CAS  Google Scholar 

  16. Gabrys D, Dörfler A, Yaromina A, et al. Effects of lovastatin alone or combined with irradiation on tumor cells in vitro and in vivo. Strahlenther Onkol 2008;184:48–53.

    Article  PubMed  Google Scholar 

  17. Hsu AL, Ching TT, Wang DS, et al. The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 2000;275:11397–403.

    Article  PubMed  CAS  Google Scholar 

  18. Jendrossek V, Handrick R, Belka C. Celecoxib activates a novel mitochondrial apoptosis signalling pathway. FASEB J 2003;17:1547–9.

    PubMed  CAS  Google Scholar 

  19. Kessler P, Grabenbauer G, Leher A, et al. [Long-term survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study.] Strahlenther Onkol 2007;183:184–9.

    Article  PubMed  Google Scholar 

  20. Kishi K, Petersen S, Petersen C, et al. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 2000;60: 1326–31.

    PubMed  CAS  Google Scholar 

  21. Kyprianou N, King ED, Bradbury D, et al. Bcl-2 overexpression delays radiation-induced apoptosis without affecting the clonogenic survival of human prostate cancer cells. Int J Cancer 1997;70:341–8.

    Article  PubMed  CAS  Google Scholar 

  22. Li JY, Wang XZ, Chen FL, et al. Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric adenocarcinoma cell line. World J Gastroenterol 2003;9:915–20.

    PubMed  CAS  Google Scholar 

  23. Lin DT, Subbaramaiah K, Shah JP, et al. Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck 2002;24:792–9.

    Article  PubMed  Google Scholar 

  24. Lin MT, Lee RC, Yang PC, et al. Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem 2001;276:48997–9002.

    Article  PubMed  CAS  Google Scholar 

  25. Liu W, Chen Y, Wang W, et al. Combination of radiation and Celebrex (celecoxib) reduce mammary and lung tumor growth. Am J Clin Oncol 2003;26:103–9.

    Article  Google Scholar 

  26. Liu XH, Yao S, Kirschenbaum A, et al. NS398, a selective cyclooxygenase-2 inhibitor, induces apoptosis and down-regulates bcl-2 expression in LNCaP cells. Cancer Res 1998;58:4245–9.

    PubMed  CAS  Google Scholar 

  27. Milas L, Furuta Y, Hunter N, et al. Dependence of indomethacin-induced potentiation of murine tumor radioresponse on tumor host immunocompetence. Cancer Res 1990;50:4473–7.

    PubMed  CAS  Google Scholar 

  28. Milas L, Gregoire V, Hunter N, et al. Radiation-induced apoptosis in tumors: effect of radiation modulating agents. Adv Exp Med Biol 1997;400B:559–64.

    PubMed  CAS  Google Scholar 

  29. Minter HA, Eveson JW, Huntley S, et al. The cyclooxygenase 2-selective inhibitor NS398 inhibits proliferation of oral carcinoma cell lines by mechanisms dependent and independent of reduced prostaglandin E2 synthesis. Clin Cancer Res 2003;9:1885–97.

    PubMed  CAS  Google Scholar 

  30. Miyamoto T, Ogino N, Yamamoto S, et al. Purification of prostaglandin endoperoxide synthetase from bovine vesicular gland microsomes. J Biol Chem 1976;251:2629–36.

    PubMed  CAS  Google Scholar 

  31. North GL. Celecoxib as adjunctive therapy for treatment of colorectal cancer. Ann Pharmacother 2001;35:1638–43.

    Article  PubMed  CAS  Google Scholar 

  32. O’Banion MK, Sadowski HB, Winn V, et al. A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 1991;266:23261–7.

    PubMed  Google Scholar 

  33. Pelzmann M, Thurnher D, Gedlicka C, et al. Nimesulide and indomethacin induce apoptosis in head and neck cancer cells. J Oral Pathol Med 2004;33:607–13.

    Article  PubMed  CAS  Google Scholar 

  34. Petersen C, Petersen S, Milas L, et al. Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 2000;6:2513–20.

    PubMed  CAS  Google Scholar 

  35. Piazuelo E, Jimenez P, Lanas A. COX-2 inhibition in esophagitis, Barrett’s esophagus and esophageal cancer. Curr Pharm Des 2003;9:2267–80.

    Article  PubMed  CAS  Google Scholar 

  36. Pyo H, Choy H, Amorino GP, et al. A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res 2001;7:2998–3005.

    PubMed  CAS  Google Scholar 

  37. Sauer R. Does aspirin reduce the risk of colorectal polyps and cancer? Strahlenther Onkol 1994;170:116–7.

    PubMed  CAS  Google Scholar 

  38. Schütze C, Dörfler A, Eicheler W, et al. Combination of EGFR/HER2 tyrosine kinase inhibition by BIBW 2992 and BIBW 2669 with irradiation in FaDu human squamous cell carcinoma. Strahlenther Onkol 2007;183:256–64.

    Article  PubMed  Google Scholar 

  39. Skvara H, Thallinger C, Wacheck V, et al. Mcl-1 blocks radiation-induced apoptosis and inhibits clonogenic cell death. Anticancer Res 2005;25: 2697–703.

    PubMed  CAS  Google Scholar 

  40. Souza RF, Spechler SJ. Barrett’s esophagus. chemoprevention. Gastrointest Endosc Clin N Am 2003;13:419–32.

    Article  PubMed  Google Scholar 

  41. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946–52.

    Article  PubMed  CAS  Google Scholar 

  42. Studer G, Luetolf UM, Glanzmann C. Locoregional failure analysis in head-and-neck cancer patients treated with IMRT. Strahlenther Onkol 2007;183:417–23.

    Article  PubMed  Google Scholar 

  43. Sun Y, Tang XM, Half E, et al. Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Cancer Res 2002;62:6323–8.

    PubMed  CAS  Google Scholar 

  44. Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J Natl Cancer Inst 1998;90:1609–20.

    Article  PubMed  CAS  Google Scholar 

  45. Tsujii M, DuBois RN. Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995;83:493–501.

    Article  PubMed  CAS  Google Scholar 

  46. Tsujii M, Kawano S, Tsuji S, et al. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998;93:705–16.

    Article  PubMed  CAS  Google Scholar 

  47. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annu Rev Med 2002;53:35–57.

    Article  PubMed  CAS  Google Scholar 

  48. Yao M, Kargman S, Lam EC, et al. Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Cancer Res 2003;63:586–92.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria

    Cornelia Czembirek, Christina Eder-Czembirek & Dritan Turhani

  2. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Vienna, Austria

    Boban M. Erovic & Dietmar Thurnher MD

  3. Department of Surgery, Research Laboratories, Medical University of Vienna, Vienna, Austria

    Andreas Spittler

  4. Department of Radiotherapy and Radiobiology and CLEXO (Center of Excellence for Clinical and Experimental Oncology), Medical University of Vienna, Vienna, Austria

    Edgar Selzer & Richard Pötter

  5. Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Währinger Guertel 18–20, 1090, Vienna, Austria

    Dietmar Thurnher MD

Authors
  1. Cornelia Czembirek
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  2. Christina Eder-Czembirek
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  3. Boban M. Erovic
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  8. Dietmar Thurnher MD
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Correspondence to Dietmar Thurnher MD.

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Czembirek, C., Eder-Czembirek, C., Erovic, B.M. et al. The Cyclooxygenase-2 Inhibitor Nimesulide, a Nonsteroidal Analgesic, Decreases the Effect of Radiation Therapy in Head-and-Neck Cancer Cells. Strahlenther Onkol 185, 310–317 (2009). https://doi.org/10.1007/s00066-009-1929-4

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  • DOI: https://doi.org/10.1007/s00066-009-1929-4

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