http://www3.interscience.wiley.com/cgi-bin/abstract/111082718/ABSTRACT
Cancer. 2005 Aug 24; [Epub ahead of print] Related Articles, Links
Zoledronic acid inhibits primary bone tumor growth in Ewing sarcoma.
Zhou Z, Guan H, Duan X, Kleinerman ES.
Division of Pediatrics, The University of Texas M. D. Anderson
Cancer Center, Houston, Texas.
email: Eugenie S. Kleinerman (ekleiner@mail.mdanderson.org)
*Correspondence to Eugenie S. Kleinerman, Division of Pediatrics, Unit
87, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe
Blvd., Houston, TX 77030, Fax: (713) 794-5042
BACKGROUND: Zoledronic acid has been shown to be effective in the
treatment of osteoporosis, hypercalcemia, and metastatic bone tumors.
The efficacy of zoledronic acid on primary bone tumors has not been
investigated. METHODS: A primary bone tumor mouse model was
established. Intratibia injection of TC71 cells resulted in an
osteolytic bone tumor. Four days after injection the mice were treated
with zoledronic acid alone, paclitaxel alone, or zoledronic acid plus
paclitaxel. Control mice were treated with phosphate-buffered saline.
Bone tumor growth was assessed using a Faxitron Specimen Radiography
System. The gene expression was detected by reverse-transcription
polymerase chain reaction (RT-PCR), ELISA, and immunohistochemistry.
Osteoclast formation was determined by tartrate-resistant acid
phosphatase (TRAP) staining. RESULTS: Zoledronic acid induced apoptosis
in TC71 human Ewing sarcoma cells and inhibited cell proliferation.
Five weeks after injection, 89% of mice in the control group developed
osteolytic bone tumors. Paclitaxel had little effect on bone tumor
growth, with 78% of mice developing tumors. By contrast, 44% of mice
treated with zoledronic acid developed bone tumors. The most effective
treatment was zoledronic acid plus paclitaxel. Tumor incidence in the
combination therapy group was only 22%. Osteoclasts were quantified
using TRAP staining. There was a decrease in TRAP-positive osteoclasts
in tumor tissues from zoledronic acid-treated animals compared to
control animals. RT-PCR, immunohistochemistry, and ELISA assay
demonstrated that zoledronic acid up-regulated osteoprotegerin
expression. CONCLUSIONS: These results suggest that zoledronic acid
induces apoptosis and inhibits primary bone tumor growth in Ewing
sarcoma through a mechanism involving the up-regulation of
osteoprotegerin. Zoledronic acid may provide a novel therapeutic
approach for the treatment of patients with Ewing sarcoma. Cancer 2005.
(c) 2005 American Cancer Society.
PMID: 16121404 [PubMed – as supplied by publisher]