The effect of non-steroidal anti-inflammatory drugs on osteosarcoma cells

L.M. Zuckerman, W.L. Frames, J.G. Elsissy, T.G. Shields, R. de Necochea-Campion, H.R. Mirshahidi, N.L. Williams, S. Mirshahidi

Department of Orthopaedic Surgery, Loma Linda University Medical Center, Loma Linda, CA, USA. wframes@llu.edu

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• Pharmacology

OBJECTIVE: Osteosarcoma (OS), an aggressive malignancy, is the most common primary bone tumor in children. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to reduce pain and inflammation. NSAIDs have shown to be toxic to certain malignancies such as colorectal, breast, and pancreatic cancers, but are not well-studied in OS. The purpose of this study is to assess whether ketorolac induces apoptosis in OS cells, compare this to indomethacin, which has been shown to inhibit OS proliferation, and explore the underlying mechanism.

MATERIALS AND METHODS: A rat OS cell line (UMR-108) was exposed to various concentrations of ketorolac and indomethacin. Cell viability, cytotoxicity, apoptosis induction, DNA fragmentation and the expression of apoptosis-related markers were examined by MTT assay, colony formation assay, flow cytometry, agarose gel electrophoresis, and Western blot respectively.

RESULTS: The results indicated that ketorolac and indomethacin could induce apoptosis of rat OS cells in a dose- and time-dependent manner. Apoptosis was confirmed by cell morphology and annexin positivity. The molecular data showed that NSAIDs affected expression of Bcl-2, survivin, and Poly (ADP-ribose) polymerase-1 (PARP).

CONCLUSIONS: These findings demonstrated that NSAIDs induced apoptosis in rat OS cells in vitro. Further research focusing on the potential cytotoxicity of NSAIDs in vivo is needed.

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