Antiproliferative effect of bupivacaine on&nbsp;patient-derived sarcoma cells

Frames,William L.; Zuckerman,Lee M.; Mirshahidi,Hamid R.; Williams,Nadine L.; Shields,Troy G.; Otoukesh,Salman; Mirshahidi,Saied

doi:10.3892/mco.2020.2077

Antiproliferative effect of bupivacaine on patient-derived sarcoma cells

Authors:
- William L. Frames
- Lee M. Zuckerman
- Hamid R. Mirshahidi
- Nadine L. Williams
- Troy G. Shields
- Salman Otoukesh
- Saied Mirshahidi
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Affiliations: Department of Orthopaedic Surgery, Loma Linda University Medical Center, Loma Linda, CA 92354, USA, Department of Surgery, Division of Orthopaedic Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA, Division of Hematology and Oncology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA, Loma Linda Cancer Center Biospecimen Laboratory, Loma Linda University Medical Center, Loma Linda, CA 92354, USA
Published online on: June 25, 2020 https://doi.org/10.3892/mco.2020.2077
Article Number: 7
Copyright: © Frames et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sarcomas are rare tumors with limited treatment options. Although chemotherapy is standard for certain subtypes, overall survival has not improved in several decades. Bupivacaine has been shown to induce apoptosis and prevent cell growth in multiple different types of malignancies but has not been studied in sarcoma. The current study evaluated the effects of bupivacaine on multiple patient‑derived sarcoma cells and a commercial sarcoma cell line. Multiple patient‑derived sarcoma cell subtypes and a commercial synovial cell sarcoma cell line were exposed to bupivacaine for different durations and at different concentrations. The patient‑derived cells included a high‑grade conventional osteosarcoma, a high‑grade undifferentiated pleomorphic sarcoma of bone, and a high‑grade synovial sarcoma. Flow cytometry and an MTT assay were used to evaluate whether a treatment effect was observed. Treatment of all the subtypes of sarcomas in this study with bupivacaine demonstrated a time‑ and dose‑dependent increase in apoptosis and decrease in cell viability. A cell viability assay demonstrated that the IC₅₀ was between 0.04 and 0.05% and that the treatment effect occurred at clinically relevant doses in vitro. Bupivacaine was toxic to both the patient‑derived cells and the commercial cell line at doses commonly used in the clinical setting. These findings provide a foundation for further in vivo studies to evaluate whether these effects will translate to the clinical setting. Although further research is necessary, bupivacaine shows promise as not only an adjunct for pain management but as a treatment modality for sarcoma.

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