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Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo

Lookup NU author(s): Dr Frida Ponthan, Dr Chris Redfern

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Abstract

Purpose: Neuroblastoma is the most common and deadly solid tumor of childhood. Cyclooxygenase-2 is expressed in clinical neuroblastoma tumors and cell lines and inhibitors of this enzyme induce apoptosis in human neuroblastoma cells in vitro and in neuroblastoma xenografts in vivo. We hypothesized that the cyclooxygenase-2- specific inhibitor celecoxib could enhance the cytotoxic effect of chemotherapeutic drugs currently used in neuroblastoma treatment. Furthermore, we investigated if prophylactic treatment with celecoxib could prevent neuroblastoma tumor development in vivo. Experimental Design: Neuroblastoma cell cytotoxicity of chemotherapeutic drugs in combination with celecoxib was examined. In vivo, athymic rats carrying established SH-SY5Y xenografts were treated with celecoxib in combination with irinotecan, doxorubicin or etoposide, or with either drug alone. For prevention studies, rats received celecoxib in the diet, 250 to 2,500 ppm, from the time of tumor cell injection. Results: Celecoxib induced a synergistic or an additive cytotoxic effect in combination with doxorubicin, etoposide, irinotecan or vincristine in vitro. In vivo, treatment with celecoxib in combination with irinotecan or doxorubicin induced a significant growth inhibition of established neuroblastoma tumors. Rats receiving celecoxib in the diet showed a distinct dose-dependent delay in tumor development compared with untreated rats. Plasma levels of celecoxib were comparable with levels obtainable in humans. Conclusions: Celecoxib potentiates the antitumor effect of chemotherapeutic drugs currently used in neuroblastoma treatment, which argues for clinical trials combining these drugs. Celecoxib could also be a potential drug for treatment of minimal residual disease. © 2007 American Association for Cancer Research.


Publication metadata

Author(s): Ponthan F, Wickström M, Gleissman H, Fuskevåg O, Segerström L, Sveinbjörnsson B, Redfern CPF, Eksborg S, Kogner P, Johnsen J

Publication type: Article

Publication status: Published

Journal: Clinical Cancer Research

Year: 2007

Volume: 13

Issue: 3

Pages: 1036-1044

Print publication date: 01/02/2007

ISSN (print): 1078-0432

ISSN (electronic): 1557-3265

URL: http://dx.doi.org/10.1158/1078-0432.CCR-06-1908

DOI: 10.1158/1078-0432.CCR-06-1908

PubMed id: 17289900


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