Dual effect of flurbiprofen on cell proliferation and agonist-induced Ca²⁺ movement in human osteosarcoma cells

In human MG63 osteosarcoma cells, the effect of flurbiprofen on intracellular Ca²⁺ concentrations ([Ca²⁺]_i) and proliferation was explored. The proliferation was enhanced by 20-120 μM flurbiprofen, and was decreased by 140-200 μM flurbiprofen. The effect of flurbiprofen on the increases in cytosolic free Ca²⁺ levels ([Ca ²⁺]_i) induced by ATP, bradykinin, histamine and thapsigargin (an inhibitor of the endoplasmic reticulum Ca²⁺ ATPase), was examined. In cell preincubated with 20 or 80 μM flurbiprofen, the [Ca²⁺]_i increases induced by all agonists were attenuated. In the presence of 20 μM flurbiprofen, the decreased [Ca²⁺] _i responses with the agonists were attributed to a defective Ca ²⁺ influx because this decrease was unobserved in agonists-induced [Ca²⁺]_i increases in the absence of extracellular Ca ²⁺. In the presence of 80 μM flurbiprofen, both the Ca ²⁺ influx component and the Ca²⁺ releasing (from organelles) component were defective. These results suggest that flurbiprofen could alter proliferation and inhibit [Ca²⁺]_i increases.