TY - JOUR
T1 - Effects of irradiation and cisplatin on human glioma spheroids
T2 - inhibition of cell proliferation and cell migration
AU - Fehlauer, Fabian
AU - Muench, Martina
AU - Rades, Dirk
AU - Stalpers, Lukas J A
AU - Leenstra, Sieger
AU - van der Valk, Paul
AU - Slotman, Ben
AU - Smid, Ernst J
AU - Sminia, Peter
PY - 2005/11
Y1 - 2005/11
N2 - PURPOSE: Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT).MATERIAL AND METHODS: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml CDDP followed by RT) was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment.RESULTS: Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed.CONCLUSION: CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.
AB - PURPOSE: Investigation of cell migration and proliferation of human glioma cell line spheroids (CLS) and evaluation of morphology, apoptosis, and immunohistochemical expression of MIB-1, p53, and p21 of organotypic muticellular spheroids (OMS) following cisplatin (CDDP) and irradiation (RT).MATERIAL AND METHODS: Spheroids of the GaMg glioma cell line and OMS prepared from biopsy tissue of six glioblastoma patients were used. Radiochemosensitvity (5 microg/ml CDDP followed by RT) was determined using migration and proliferation assays on CLS. In OMS, histology and immunohistochemical studies of MIB-1, p53, and p21 expression were examined 24 and 48 h following treatment.RESULTS: Combination treatment led to a migration inhibition of 38% (CDDP 13%; RT 27%) and specific growth delay of 2.6 (CDDP 1.3; RT 2.1) in CLS. Cell cycle analysis after combination treatment showed an accumulation of cells in the G2/M phase. In OMS, apoptosis increased, cell proliferation decreased, and p53/p21 expression increased more pronounced following CDDP+RT. No morphological damage was observed.CONCLUSION: CDDP can lead to enhancement of the RT effect in spheroids of both human glioma cell line spheroids and biopsy spheroids from glioblastoma specimens. The exerted effect is additive rather than synergistic.
KW - Antineoplastic Agents/pharmacology
KW - Apoptosis/drug effects
KW - Biomarkers, Tumor/metabolism
KW - Cell Line, Tumor
KW - Cell Movement/drug effects
KW - Cell Proliferation/drug effects
KW - Chemotherapy, Adjuvant
KW - Cisplatin/pharmacology
KW - Cyclin-Dependent Kinase Inhibitor p21/metabolism
KW - Flow Cytometry
KW - Gene Expression Regulation, Neoplastic
KW - Glioma/drug therapy
KW - Humans
KW - Immunohistochemistry
KW - Ki-67 Antigen/metabolism
KW - Radiotherapy, Adjuvant
KW - Spheroids, Cellular
KW - Time Factors
KW - Tumor Suppressor Protein p53/metabolism
U2 - 10.1007/s00432-005-0014-3
DO - 10.1007/s00432-005-0014-3
M3 - Article
C2 - 16096850
SN - 0171-5216
VL - 131
SP - 723
EP - 732
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
IS - 11
ER -