Document Detail


Differential cyclooxygenase-2 enzyme expression in radiosensitive versus radioresistant glioblastoma multiforme cell lines.
MedLine Citation:
PMID:  15816645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Glioblastoma multiforme (GBM) is a high-grade primary brain tumor that is refractory to current forms of treatment. In cell studies, the growth rate of GBM cells correlates with the level of Cyclooxygenase-2 (COX-2) enzyme expression. COX-2 has been implicated in carcinogenesis of systemic cancers. Recently, COX-2 inhibition has been shown to increase the radiosensitivity of various tumors. We wished to assess whether the expression of COX-2 is greater in radioresistant versus radiosensitive forms of GBM. MATERIALS AND METHODS: The radiosensitive (A172) and radioresistant (T98G) Glioblastoma multiforme cell lines were assayed for COX-2 expression using standard immunofluorescence histochemistry. Fluorescence readings were recorded per field. Western blot analysis was performed on both A172 and T98G GBM cell lines. The radioresistant cells were exposed to incremental doses of radiation in the presence and absence of a COX-2-selective inhibitor. Radioresistant cells were then exposed to incremental doses of COX-2-selective inhibitor at a constant dose of radiation. RESULTS: The radioresistant cell line T98G had an approximate 1. 7-fold greater expression of COX-2 than did the radiosensitive cell line A172, as per immunofluorescence histochemistry. Western blot analysis confirmed this finding. Statistical analysis (Bonferroni/Dunn) showed the results to be significant (p<0.0001). The wells containing radioresistant cells exposed to incremental doses of radiation and COX-2 inhibitors appeared to have higher cell kill when compared to radiation alone. Furthermore, increasing the COX-2 inhibitor concentration yielded higher cell kill. CONCLUSION: The results presented here show that the radioresistant GBM cell line, T98G, has a greater expression of COX-2 than does the radiosensitive GBM cell line, A172. These results suggest that: (i) COX-2 expression may serve as a marker for assessing radioresistance in GBM, (ii) COX-2 inhibition may lower the required doses of postoperative radiation, (iii) COX-2 inhibitors may have a role in radiosensitizing otherwise radioresistant forms of GBM.
Authors:
Aftab Karim; Kevin McCarthy; Ajay Jawahar; Donald Smith; Brian Willis; Anil Nanda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  25     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2005 Jan-Feb
Date Detail:
Created Date:  2005-04-08     Completed Date:  2005-05-03     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  675-9     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Louisiana State University Health Sciences Center in Shreveport, Shreveport, Louisiana 71130-3932, USA.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Western
Brain Neoplasms / enzymology*,  radiotherapy*
Cell Death
Cell Line, Tumor
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / pharmacology
Glioblastoma / enzymology*,  radiotherapy*
Humans
Immunoblotting
Immunohistochemistry
Membrane Proteins
Microscopy, Fluorescence
Prostaglandin-Endoperoxide Synthases / biosynthesis*
Radiation Tolerance*
Time Factors
Chemical
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 0/Cyclooxygenase Inhibitors; 0/Membrane Proteins; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases

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