Efficacy of zoledronate against neuroblastoma.
BACKGROUND
We investigated the antitumor and antiosteoclastic effects of zoledronate against human neuroblastoma in vitro and in a murine model of bone metastasis.


METHODS
Antitumor activity of zoledronate against neuroblastoma cell lines was assessed by evaluating proliferation, apoptosis, and cell-cycle progression. A murine model of bone invasion was used to assess antiosteoclastic and antitumor activity in vivo. Mice were followed by radiographic and bioluminescence imaging.


RESULTS
Treatment of human neuroblastoma cells resulted in a decrease in cell count, increase in apoptosis, and arrest of cell-cycle progression. In the model of bone invasion, mice were treated weekly with zoledronate or vehicle control 10 days after tumor cell inoculation. Five weeks later, radiographs revealed a large degree of osteolytic disease in control mice. Impressively, mice treated with zoledronate demonstrated minimal radiographic changes at this time. Bioluminescence imaging of these mice revealed a significant restriction of tumor growth during the course of therapy.


CONCLUSIONS
Zoledronate exhibits significant antitumor activity against human neuroblastoma cells in vitro, prevents development of osteolytic lesions, and restricts tumor growth in a murine model of bone metastasis. These results suggest that clinical investigation of zoledronate or similar bisphosphonates as adjuvant therapy in neuroblastoma patients is warranted.
Dickson
Paxton V
PV
Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hamner
John B
JB
Cauthen
Lindsey A
LA
Ng
Catherine Y C
CY
McCarville
M Beth
MB
Davidoff
Andrew M
AM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid