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Effects of the proteasome inhibitor bortezomib on osteolytic human prostate cancer cell metastases

Prostate Cancer and Prostatic Diseases volume 8, pages 327–334 (2005)Cite this article

Abstract

Prostate adenocarcinoma is the most common malignancy diagnosed in males, and bone metastases remain a significant source of morbidity and mortality in this population. The ubiquitin-proteasome cascade is responsible for the degradation of intracellular proteins, and this pathway is thought to play an essential role in the development of malignancies by altering the levels of various proteins involved in the regulation of cell division. Proteasome inhibitors represent a class of chemotherapeutic agents that have been shown to inhibit tumor growth by a number of different mechanisms. Using a murine intratibial injection model, we examined the effects of the proteasome inhibitor bortezomib on the establishment and progression of osteolytic bone lesions induced by human CaP cells (PC-3 cell line). In this study, the intravenous administration of bortezomib (1 mg/kg) did not prevent the initial formation of osteolytic lesions but did appear to inhibit their growth in a time-dependent fashion. In contrast, bortezomib therapy effectively inhibited the establishment and progression of subcutaneous PC-3 tumors, which served as a positive control. These results suggest that proteasome inhibitors such as bortezomib may represent a novel adjunctive therapy for the treatment of osteolytic skeletal metastases, especially when treatment is initiated early during the disease process.

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Acknowledgements

This study was supported by a research grant from the National Institutes of Health (R-01 CA-103039:01 (JRL)) and CaPCURE (JRL). We also thank Millennium Pharmaceuticals Inc., for generously providing the bortezomib used in this study as well as Fred Dorey, PhD, for his assistance with the statistical analyses.

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  1. Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    P G Whang, S C Gamradt, J J Gates & J R Lieberman

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  1. P G Whang
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  3. J J Gates
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  4. J R Lieberman
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Correspondence to J R Lieberman.

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Whang, P., Gamradt, S., Gates, J. et al. Effects of the proteasome inhibitor bortezomib on osteolytic human prostate cancer cell metastases. Prostate Cancer Prostatic Dis 8, 327–334 (2005). https://doi.org/10.1038/sj.pcan.4500823

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