Objective—To determine the effect of pamidronate
disodium on the in vitro viability of osteosarcoma
cells and non-neoplastic cells from dogs.
Sample Population—3 osteosarcoma and 1 fibroblast
cell lines derived from dogs.
Procedure—Cell counts and cell viability assays were
performed in cultures of osteosarcoma cells (POS,
HMPOS, and COS31 cell lines) and fibroblasts after
24, 48, and 72 hours of incubation with pamidronate
at concentrations of 0.001 to 1,000µM or with no
drug (control treatment). Percentage viability was
determined in cell samples for each concentration of
pamidronate and each incubation time. A DNA fragmentation
analysis was performed to assess bisphosphonate-
Results—Osteosarcoma cell viability decreased significantly
in a concentration- and time-dependent
manner at pamidronate concentrations ranging from
100 to 1,000µM, most consistently after 48 and 72
hours' exposure. In treated osteosarcoma cells, the
lowest percentage cell viability was 34% (detected
after 72 hours' exposure to 1,000µM pamidronate).
Conversely, 72 hours' exposure to 1,000µM
pamidronate did not significantly reduce fibroblast viability
(the lowest percentage viability was 76%). After
72 hours of exposure, pamidronate did not cause
DNA fragmentation in POS or HMPOS cells.
Conclusions and Clinical Relevance—Results indicate
that pamidronate may have the potential to inhibit
osteosarcoma growth in dogs, possibly through a
nonapoptotic mechanism. The clinical relevance of
these in vitro findings remains to be determined, but
administration of pamidronate may potentially be indicated
as an adjuvant treatment in chemotherapeutic
protocols used in dogs. (Am J Vet Res 2005;66:
Objective—To determine whether exposure of
canine osteosarcoma cells to deracoxib or piroxicam
results in decreased viability, whether the cytotoxic
effects of deracoxib and piroxicam involve induction
of apoptosis, and whether deracoxib is a more
potent inhibitor of osteosarcoma cell growth than
Sample Population—1 fibroblast and 3 osteosarcoma
Procedure—Cell counts and viability assays were
performed using osteosarcoma cells (POS, highly
metastatic POS, and canine osteosarcoma cell 31)
and fibroblasts after 72 hours of incubation with deracoxib
at concentrations of 0.5µM to 500µM or piroxicam
at concentrations of 1µM to 1,000µM.
Percentage viability was determined for each concentration.
A DNA fragmentation analysis was performed
to assess drug-induced apoptosis.
Results—Concentration of deracoxib required for
50% inhibition of cell viability (IC50) was reached in all
3 osteosarcoma cell lines and ranged from 70 to
150µM, whereas the IC50 for piroxicam was only
reached in the POS cell line at 500µM. Neither deracoxib
nor piroxicam induced sufficient toxicity in
fibroblasts to reach an IC50. Exposure of osteosarcoma
cells to cytotoxic concentrations of deracoxib and
piroxicam did not result in DNA fragmentation.
Conclusions and Clinical Relevance—Intermediate
and high concentrations of deracoxib and high concentrations
of piroxicam were cytotoxic to osteosarcoma
cells; neither drug inhibited cell viability at typical
plasma concentrations in dogs. Deracoxib inhibited
viability of cells at concentrations that did not
affect fibroblast viability. There was no evidence of
apoptosis induction for either drug; however, only 1
cell line was evaluated for apoptosis induction and
only for a limited selection of drug concentrations.
(Am J Vet Res 2005;66:1961–1967)