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The In Vitro Effects of Bupivacaine on Cartilage-forming Tumor Cells

Chapman, Garrett L., MD; Zuckerman, Lee M., MD; Mirshahidi, Saied, MSc, PhD

JAAOS - Journal of the American Academy of Orthopaedic Surgeons: April 1, 2019 - Volume 27 - Issue 7 - p e337–e345
doi: 10.5435/JAAOS-D-17-00407
Research Article

Introduction: Bupivacaine is a commonly used local anesthetic that has been shown to be cytotoxic to articular chondrocytes and various tumor cells. This study evaluates the in vitro effects of bupivacaine on cartilaginous tumor cells.

Methods: Multiple different cartilaginous tumors were evaluated, including enchondromas, chondroblastomas, a low-grade chondrosarcoma, which were harvested from patients during tumor resection, and a grade-II chondrosarcoma SW1535 (ATCC HTB-94). The tumor cells were treated with 0.25% and 0.5% bupivacaine at various times points, and the result was compared with that of untreated tumor cells. Tumor cell viability and apoptosis were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and flow cytometry.

Results: The tumors were analyzed in groups according to their pathologic diagnosis. Increasing periods of exposure to bupivacaine decreased the cell viability in all tumor samples. The cytotoxicity of 0.5% bupivacaine was significantly greater than that of 0.25% bupivacaine in all tumor cells tested.

Discussion: At clinically relevant concentrations, in vitro exposure to bupivacaine caused a decrease in cellular viability and an increase in the induction of apoptosis in a dose- and time-dependent manner in each of the tumor cells evaluated in this study.

From the Department of Orthopaedic Surgery (Dr. Chapman and Dr. Zuckerman), Loma Linda University Health, and the Department of Medicine & Basic Science (Dr. Mirshahidi), Loma Linda University Cancer Center, Biospecimen Laboratory, Loma Linda, CA.

Correspondence to Dr. Zuckerman:

This work was performed with funding from the Department of Orthopaedic Surgery at the Loma Linda University Medical Center and the Loma Linda University School of Medicine Dean's Office for the Grants to Promote Collaborative and Translational Research (GCAT 2016, #681163).

Dr. Zuckerman is a consultant for NuVasive Specialized Orthopedics and a committee member for the AAOS. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Chapman, Dr. Zuckerman, and Dr. Mirshahidi.

© 2019 by American Academy of Orthopaedic Surgeons
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