In Vitro Studies on the Influence of Meloxicam on Cytotoxic Activity Induced by Risedronate Sodium in Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines

SIMPLE SUMMARY: The aim of this in vitro study was to reveal the pharmacological interactions between meloxicam and risedronate sodium, used jointly to induce a cytotoxic effect in canine (D-17) and human (U-2 OS) osteosarcoma cell lines. Meloxicam, a non-steroidal anti-inflammatory drug, is capable of intensifying the cytotoxic activity of risedronate sodium routinely used in bone tissue metabolic diseases. The cell cultures were incubated, tested, and evaluated according to standard protocols. The study demonstrated a greater susceptibility of canine osteosarcoma cells in vitro to the investigated drug combination than the human. In both cases, meloxicam alone showed low cytotoxic activity against the tested cell lines, but the two compounds combined were synergic. ABSTRACT: The study describes the cytotoxic effect against human and canine osteosarcoma (U-2 OS and D-17) cell lines induced by risedronate sodium and meloxicam per se and in combination. Both cell lines were prepared according to standard procedures for cell cultures studies. The cell viability was estimated in both cell lines treated with chosen concentrations of risedronate sodium and meloxicam. The apoptosis assessment was carried out using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. EC(50) values, computed for risedronate sodium and meloxicam cytotoxicity, showed comparable effects against the canine OS cell line in similar concentration of both drugs. In case of human OS, the stronger cytotoxic effect of risedronate sodium was proved. The EC(50) values for meloxicam in both cell lines were, statistically, significantly different (* p < 0.05). Moreover, the cytotoxic effect of a combined administration of meloxicam and risedronate sodium in doses 100 µg/mL, compared with the negative control showed statistically significant differences. The human OS cell line was more resistant to both compounds than the canine OS cell line. The apoptotic effect in canine and human osteosarcoma triggered by risedronate sodium and meloxicam was statistically significant (p < 0.05). The cytotoxic effect induced with 100 µg/mL of risedronate sodium proved statistically significant differences between both tested cell lines compared to negative control. The results obtained with 10 and 100 µg/mL of meloxicam were not statistically significant. The study showed the synergic mechanism of action of risedronate sodium and meloxicam, but the concentrations used in vitro will not be possible to achieve in in vivo. Therefore, our results serve as basis only to design future studies on the tissue level.