Objective: To determine the in vitro effects of the proteasome inhibitor bortezomib in feline injection site sarcoma (FISS) cell lines.
Sample: In vitro cultures of the FISS cell lines Ela-1, Hamilton, and Kaiser.
Procedures: Cells were treated with increasing doses of bortezomib or vehicle alone (dimethyl sulfoxide) and evaluated for cell viability via an adenosine triphosphate concentration assay, proteasome activity via a commercially available proteasome assay, accumulation of ubiquitinated proteins via Western blot, and apoptosis via flow cytometry.
Results: All 3 cell lines were sensitive to bortezomib with a 50% inhibitory concentration after 48 hours of treatment at 17.46 nM (95% CI, 15.47 to 19.72 nM) for Ela-1, 19.48 nM (95% CI, 16.52 to 23.00 nM) for Hamilton, and 21.38 nM (95% CI, 19.24 to 23.78 nM) for Kaiser. In the Ela-1 cell line, 20 nM bortezomib inhibited 20S proteasome activity by 90.9% compared with the vehicle-only control. In the Kaiser cell line, 20 nM bortezomib decreased 20S proteasome activity by 70%, compared with the untreated vehicle-only control. Last, treatment with bortezomib (25 and 40 nM) resulted in statistically significant decreases in viable cells accompanied by a statistically significant increase in apoptotic cells.
Clinical relevance: Treatment options for FISS, especially nonresectable FISS, are currently very limited. These results support further investigation of bortezomib either alone or in combination with other treatments in such cases.