title: High-LET radiation combined with oxaliplatin induce autophagy in U-87 glioblastoma cells.
abstract: Modern protocols of concomitant chemo/radiotherapy provide a very effective strategy to treat certain types of tumors. High-linear energy transfer (LET) radiations, on the other hand, have an increased efficacy against cancer with low radiosensibility and critical localization. We previously reported that oxaliplatin, a third generation platinum drug, was able to reinforce the cytotoxicity of an irradiation by fast neutrons towards human glioblastoma U-87 cells in culture. We show here that such a combination has the capacity to enhance the number of double strand breaks in DNA and to induce autophagy in these cells. Xenografts experiments were further performed in nude mice subcutaneously transplanted with U-87 cells. When injected shortly before a single irradiation by fast neutrons, oxaliplatin causes a marked reduction of tumor growth compared with the irradiation alone. Overall, our data indicate the unique cytotoxic mechanism of a combined high-LET irradiation and oxaliplatin treatment modality and suggest its potential application in anticancer therapy.
authors.affiliation: Laboratoire de Cancérologie Expérimentale et de Radiobiologie, EA-3430, Université Louis Pasteur, Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Hôpitaux Universitaires, 1 place de l'Hôpital, Strasbourg, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Benzina
authors.forename: Anaïs
authors.initials: A
authors.lastname: Altmeyer
authors.forename: Faten
authors.initials: F
authors.lastname: Malek
authors.forename: Patrick
authors.initials: P
authors.lastname: Dufour
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Denis
authors.forename: John
authors.initials: J
authors.lastname: Gueulette
authors.forename: Pierre
authors.initials: P
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001343:Autophagy / Q000528:radiation effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D005214:Fast Neutrons; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D018499:Linear Energy Transfer; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin