title: Combined effects of bisphosphonate and radiation on osteosarcoma cells.
abstract: Antitumour effects of third-generation bisphosphonates (BPs), such as zoledronic acid (ZOL), and the combined effects of ZOL with other anticancer agents against osteosarcoma cells have been reported previously. The aim of this study was to identify further combined antitumour effects using BPs and radiation in osteosarcoma cell lines.
  
  
  METHODS
  Cell proliferation, cell cycle analysis, and nuclear morphology were examined in each osteosarcoma cell line divided into three groups (ZOL alone, radiation alone and the ZOL/radiation combination).
  
  
  RESULTS
  Combined therapy (low-concentration ZOL and low-dose radiation) had significant growth inhibitory effects compared to the use of ZOL or radiation individually. Flow cytometric analysis revealed an increase in cells in the sub-G(1) phase by combined treatment, and apoptotic cells were also observed.
  
  
  CONCLUSIONS
  These findings suggest that combination therapy using BPs and radiation may be a promising therapy for osteosarcoma, producing fewer side effects and complications in the near future.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ryu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Murata
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Koto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Horie
authors.forename: Takaaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nishigaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sakabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeshita
authors.forename: Megumi
authors.initials: M
authors.lastname: Itoi
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D048708:Cell Growth Processes / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid