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Zoledronic acid inhibits osteosarcoma growth in an orthotopic model

Dass, Crispin R and Choong, Peter F. M (2007) Zoledronic acid inhibits osteosarcoma growth in an orthotopic model. Molecular Cancer Therapeutics, 6. pp. 3263-3270. ISSN 1535-7163

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Abstract

Zoledronic acid (ZOL) has been shown to reduce osteolysis in bone metastasis. Its efficacy in osteosarcoma has not been convincingly proved in a clinically relevant model for the disease. In vitro, ZOL decreased osteosarcoma cell proliferation, mainly due to an increase in apoptosis in a dose-dependent fashion. There was a decrease in cell migration at ≥10 μmol/L concentrations, but invasion was inhibited at a much lower dose of 0.1 μmol/L. Reverse transcription-PCR showed that ZOL overall caused an increased expression of osteocalcin and decreased expression of alkaline phosphatase, osteopontin, osteonectin, and vascular endothelial growth factor, with no change in expression of osteoprotegerin. ZOL administration s.c. twice weekly at 0.12 mg/kg to SaOS-2 tumor–bearing mice resulted in primary tumor growth inhibition, reduction in lung metastases, and dramatic decrease in osteolysis. Furthermore, in the ZOL cohort, there was a clear reduction in the number of osteoclasts in bone exposed to tumor and a lower tumor vessel density. These data point to the adjuvant potential of ZOL in the management of osteosarcoma not only for its antiosteolytic properties but also for its ability to directly halt tumor cell growth and metastasis via its effects on viability, invasion, differentiation, and angiogenesis.

Item Type: Article
Uncontrolled Keywords: ResPubID18884, osteosarcoma, zoledronic acid, apoptosis, metastasis, differentiation, angiogenesis
Subjects: FOR Classification > 1112 Oncology and Carcinogenesis
FOR Classification > 0601 Biochemistry and Cell Biology
Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
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Depositing User: VUIR
Date Deposited: 09 May 2012 06:45
Last Modified: 16 Dec 2014 05:41
URI: http://vuir.vu.edu.au/id/eprint/3230
DOI: 10.1158/1535-7163.MCT-07-0546
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Citations in Scopus: 44 - View on Scopus

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