The cytotoxicity of high-linear energy transfer radiation is reinforced by oxaliplatin in human glioblastoma cells.
The combination of high-linear energy transfer (LET) radiation with chemotherapeutic agents may offer new perspectives in cancer treatment. We therefore assessed the consequences of a treatment in which U-87 human glioblastoma cells were irradiated with p(65)+Be neutrons in the presence of oxaliplatin, a third generation platinum anticancer drug having higher apoptosis-inducing activity than cisplatin. Cell survival, apoptosis, cell cycle progression as well as p21 and p53 protein expressions were analyzed. Results show that an enhanced cytotoxic effect was obtained when the two treatments were combined and that, unlike what we previously observed with cisplatin, this was not due to a reinforcement of apoptosis. Altogether, our results also indicate the potential of oxaliplatin for use in association with high-LET radiation against tumors refractory to conventional photon radiotherapy.
Benzina
Sami
S
Laboratoire de Cancérologie Expérimentale et de Radiobiologie, EA-3430, IRCAD, Hôpitaux Universitaires, 1 Place de l'Hôpital, Strasbourg, France.
Debomy
Frederic
F
Bergerat
Jean-Pierre
JP
Denis
Jean-Marc
JM
Gueulette
John
J
Dufour
Patrick
P
Bischoff
Pierre
P
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018499:Linear Energy Transfer; D009502:Neutrons; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; D000077150:Oxaliplatin; D053148:Caspase 3