Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition: independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration

Gitta K Kuipers, Ben J Slotman, Laurine E Wedekind, T Rianne Stoter, Jaap van den Berg, Peter Sminia, M Vincent M Lafleur

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: Patients with a malignant glioma have a very poor prognosis. Cyclooxygenase-2 (COX-2) protein is regularly upregulated in gliomas and might be a potential therapeutic target. The effects of three selective COX-2 inhibitors were studied on three human glioma cell lines.

MATERIALS AND METHODS: The selective COX-2 inhibitors NS-398, Celecoxib and Meloxicam and three human glioma cell lines (D384, U251 and U87) were used. Cell growth was assessed by a proliferation assay, the interaction with radiation (0 - 6 Gy) was studied using the clonogenic assay and cell cycle distribution was determined by FACS (fluorescence-activated cell sorting) analysis.

RESULTS: All COX-2 inhibitors reduced proliferation of the glioma cell lines irrespective of their COX-2 expression level. Incubation with 200 microM NS-398 24 h before radiation enhanced radiation-induced cell death of D384 cells and 750 microM Meloxicam resulted in radiosensitization of D384 and U87 cells. No radiosensitization was observed with COX-2 inhibitor administration after radiotherapy. Treatment of D384 with NS-398 (200 microM) or Celecoxib (50 microM) and U87 with NS-398 (200 microM) after radiation resulted even in radioprotection.

CONCLUSIONS: Effectiveness of COX-2 inhibitors on cell proliferation and radio-enhancement was independent of COX-2 protein expression. The sequence of COX-2 inhibitor addition and irradiation is very important.

Original languageEnglish
Pages (from-to)677-85
Number of pages9
JournalInternational Journal of Radiation Biology
Volume83
Issue number10
DOIs
Publication statusPublished - Oct 2007

Cite this

@article{efbd3dfb1a2d4702a1539651cfb4db7d,
title = "Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition: independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration",
abstract = "PURPOSE: Patients with a malignant glioma have a very poor prognosis. Cyclooxygenase-2 (COX-2) protein is regularly upregulated in gliomas and might be a potential therapeutic target. The effects of three selective COX-2 inhibitors were studied on three human glioma cell lines.MATERIALS AND METHODS: The selective COX-2 inhibitors NS-398, Celecoxib and Meloxicam and three human glioma cell lines (D384, U251 and U87) were used. Cell growth was assessed by a proliferation assay, the interaction with radiation (0 - 6 Gy) was studied using the clonogenic assay and cell cycle distribution was determined by FACS (fluorescence-activated cell sorting) analysis.RESULTS: All COX-2 inhibitors reduced proliferation of the glioma cell lines irrespective of their COX-2 expression level. Incubation with 200 microM NS-398 24 h before radiation enhanced radiation-induced cell death of D384 cells and 750 microM Meloxicam resulted in radiosensitization of D384 and U87 cells. No radiosensitization was observed with COX-2 inhibitor administration after radiotherapy. Treatment of D384 with NS-398 (200 microM) or Celecoxib (50 microM) and U87 with NS-398 (200 microM) after radiation resulted even in radioprotection.CONCLUSIONS: Effectiveness of COX-2 inhibitors on cell proliferation and radio-enhancement was independent of COX-2 protein expression. The sequence of COX-2 inhibitor addition and irradiation is very important.",
keywords = "Celecoxib, Cell Line, Tumor/drug effects, Cell Proliferation/drug effects, Cyclooxygenase 2/genetics, Cyclooxygenase 2 Inhibitors/pharmacology, Dose-Response Relationship, Radiation, Flow Cytometry/methods, Gene Expression Regulation, Neoplastic, Glioma/pathology, Humans, Neoplasms/drug therapy, Nitrobenzenes/pharmacology, Pyrazoles/pharmacology, Radiation-Protective Agents/pharmacology, Sulfonamides/pharmacology, Thiazines/pharmacology, Thiazoles/pharmacology",
author = "Kuipers, {Gitta K} and Slotman, {Ben J} and Wedekind, {Laurine E} and Stoter, {T Rianne} and Berg, {Jaap van den} and Peter Sminia and Lafleur, {M Vincent M}",
year = "2007",
month = "10",
doi = "10.1080/09553000701558985",
language = "English",
volume = "83",
pages = "677--85",
journal = "International Journal of Radiation Biology",
issn = "0955-3002",
publisher = "Informa Healthcare",
number = "10",

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Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition : independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration. / Kuipers, Gitta K; Slotman, Ben J; Wedekind, Laurine E; Stoter, T Rianne; Berg, Jaap van den; Sminia, Peter; Lafleur, M Vincent M.

In: International Journal of Radiation Biology, Vol. 83, No. 10, 10.2007, p. 677-85.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Radiosensitization of human glioma cells by cyclooxygenase-2 (COX-2) inhibition

T2 - independent on COX-2 expression and dependent on the COX-2 inhibitor and sequence of administration

AU - Kuipers, Gitta K

AU - Slotman, Ben J

AU - Wedekind, Laurine E

AU - Stoter, T Rianne

AU - Berg, Jaap van den

AU - Sminia, Peter

AU - Lafleur, M Vincent M

PY - 2007/10

Y1 - 2007/10

N2 - PURPOSE: Patients with a malignant glioma have a very poor prognosis. Cyclooxygenase-2 (COX-2) protein is regularly upregulated in gliomas and might be a potential therapeutic target. The effects of three selective COX-2 inhibitors were studied on three human glioma cell lines.MATERIALS AND METHODS: The selective COX-2 inhibitors NS-398, Celecoxib and Meloxicam and three human glioma cell lines (D384, U251 and U87) were used. Cell growth was assessed by a proliferation assay, the interaction with radiation (0 - 6 Gy) was studied using the clonogenic assay and cell cycle distribution was determined by FACS (fluorescence-activated cell sorting) analysis.RESULTS: All COX-2 inhibitors reduced proliferation of the glioma cell lines irrespective of their COX-2 expression level. Incubation with 200 microM NS-398 24 h before radiation enhanced radiation-induced cell death of D384 cells and 750 microM Meloxicam resulted in radiosensitization of D384 and U87 cells. No radiosensitization was observed with COX-2 inhibitor administration after radiotherapy. Treatment of D384 with NS-398 (200 microM) or Celecoxib (50 microM) and U87 with NS-398 (200 microM) after radiation resulted even in radioprotection.CONCLUSIONS: Effectiveness of COX-2 inhibitors on cell proliferation and radio-enhancement was independent of COX-2 protein expression. The sequence of COX-2 inhibitor addition and irradiation is very important.

AB - PURPOSE: Patients with a malignant glioma have a very poor prognosis. Cyclooxygenase-2 (COX-2) protein is regularly upregulated in gliomas and might be a potential therapeutic target. The effects of three selective COX-2 inhibitors were studied on three human glioma cell lines.MATERIALS AND METHODS: The selective COX-2 inhibitors NS-398, Celecoxib and Meloxicam and three human glioma cell lines (D384, U251 and U87) were used. Cell growth was assessed by a proliferation assay, the interaction with radiation (0 - 6 Gy) was studied using the clonogenic assay and cell cycle distribution was determined by FACS (fluorescence-activated cell sorting) analysis.RESULTS: All COX-2 inhibitors reduced proliferation of the glioma cell lines irrespective of their COX-2 expression level. Incubation with 200 microM NS-398 24 h before radiation enhanced radiation-induced cell death of D384 cells and 750 microM Meloxicam resulted in radiosensitization of D384 and U87 cells. No radiosensitization was observed with COX-2 inhibitor administration after radiotherapy. Treatment of D384 with NS-398 (200 microM) or Celecoxib (50 microM) and U87 with NS-398 (200 microM) after radiation resulted even in radioprotection.CONCLUSIONS: Effectiveness of COX-2 inhibitors on cell proliferation and radio-enhancement was independent of COX-2 protein expression. The sequence of COX-2 inhibitor addition and irradiation is very important.

KW - Celecoxib

KW - Cell Line, Tumor/drug effects

KW - Cell Proliferation/drug effects

KW - Cyclooxygenase 2/genetics

KW - Cyclooxygenase 2 Inhibitors/pharmacology

KW - Dose-Response Relationship, Radiation

KW - Flow Cytometry/methods

KW - Gene Expression Regulation, Neoplastic

KW - Glioma/pathology

KW - Humans

KW - Neoplasms/drug therapy

KW - Nitrobenzenes/pharmacology

KW - Pyrazoles/pharmacology

KW - Radiation-Protective Agents/pharmacology

KW - Sulfonamides/pharmacology

KW - Thiazines/pharmacology

KW - Thiazoles/pharmacology

U2 - 10.1080/09553000701558985

DO - 10.1080/09553000701558985

M3 - Article

VL - 83

SP - 677

EP - 685

JO - International Journal of Radiation Biology

JF - International Journal of Radiation Biology

SN - 0955-3002

IS - 10

ER -