Combined effects of bisphosphonate and radiation on osteosarcoma cells.
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.
Ryu
Kazuteru
K
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Murata
Hiroaki
H
Koto
Kazutaka
K
Horie
Naoyuki
N
Matsui
Takaaki
T
Nishigaki
Yasunori
Y
Sakabe
Tomoya
T
Takeshita
Hideyuki
H
Itoi
Megumi
M
Kimura
Shinya
S
Ashihara
Eishi
E
Maekawa
Taira
T
Fushiki
Shinji
S
Kubo
Toshikazu
T
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
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid