Document Detail


Celecoxib prevents neuroblastoma tumor development and potentiates the effect of chemotherapeutic drugs in vitro and in vivo.
MedLine Citation:
PMID:  17289900     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Frida Ponthan; Malin Wickström; Helena Gleissman; Ole M Fuskevåg; Lova Segerström; Baldur Sveinbjörnsson; Christopher P F Redfern; Staffan Eksborg; Per Kogner; John I Johnsen
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  13     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-09     Completed Date:  2007-05-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1036-44     Citation Subset:  IM    
Affiliation:
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Apoptosis
Cell Line, Tumor
Cyclooxygenase 2 / biosynthesis*
Cyclooxygenase Inhibitors / pharmacology
Humans
Ki-67 Antigen / biosynthesis
Male
Neoplasm Transplantation
Neuroblastoma / drug therapy*,  metabolism
Pyrazoles / therapeutic use*
Rats
Rats, Nude
Sulfonamides / therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cyclooxygenase Inhibitors; 0/Ki-67 Antigen; 0/Pyrazoles; 0/Sulfonamides; 169590-42-5/celecoxib; EC 1.14.99.1/Cyclooxygenase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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