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
C2 - 17729162
VL - 83
SP - 677
EP - 685
JO - International Journal of Radiation Biology
JF - International Journal of Radiation Biology
SN - 0955-3002
IS - 10
ER -