Induction of apoptosis or necrosis by ionizing radiation is dose-dependent in MG-63 osteosarcoma multicellular spheroids.
This study investigates cell growth and death (apoptosis and necrosis) in actively proliferating MG-63 osteosarcoma spheroids in response to two doses of ionizing radiation (5 and 30 Gy). Cell growth was examined by growth curves and by cell cycle analyses utilizing flow cytometry. Death was examined in both disaggregated and whole spheroids by the chromatin dye Hoechst and by Western blot analysis of the bcl-2 family of proteins known to be involved in the apoptotic process. The results indicate that after exposure to 5 Gy MG-63 spheroids die by apoptosis, while after exposure to 30 Gy they die by necrosis. The analysis of the bcl-2 family of proteins demonstrates that bcl-2, bax and bcl-XL are involved in triggering apoptosis in spheroids exposed to 5 Gy. The possibility of studying the mechanisms responsible for radiation-induced cell death in three-dimensional spheroids (which represent much more closely in vivo tumors) is extremely important if the foundations for more selective and controllable clinical radiotherapeutic protocols are to be laid.
Rainaldi
Gabriella
G
Laboratorio di Ultrastrutture, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Ferrante
Antonella
A
Indovina
Pietro Luigi
PL
Santini
Maria Teresa
MT
D017209:Apoptosis / Q000528:radiation effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D009336:Necrosis; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018874:Spheroids, Cellular / Q000473:pathology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein