CYTOTOXICITY OF GALLIUM NITRATE IN VITRO USING BLADDER CANCER CELLS

Abstract

Gallium nitrate has been used systemically for some malignancies in clinical trials. Because bladder cancer has many transferrin (Tf) receptors and gallium has been reported to bind avidly with Tf receptors, gallium cytotoxicity and the possibility of intravesical instillation therapy with gallium nitrate were studied in vitro. The bladder cancer cell lines J82, 639V, VMCuB1, SCaBER, and 5637 were used. The amount of Tf receptor was checked by a rosette assay. As a cytotoxicity assay, two experimental models were tested using two or 72 hours of exposure to gallium solution. A gallium release study using 67Ga was done to investigate the movement of incorporated gallium. J82 had the most and SCaBER had the least Tf receptors. For 72 hours of exposure at gallium concentrations above 250 mumol/L, the inhibitory effect was a function of gallium concentration, and 100% cytotoxicity occurred at 2 mmol/L. At lower concentrations of gallium, the effect was related to the amount of Tf and the level of Tf receptor expression of the cells. With two hours of exposure, which was assumed to be a model of intravesical therapy, the inhibitory effect increased in proportion to gallium concentration and the frequency of treatment. Twenty mmol/L gallium effectively inhibited the growth in two hours of exposure. Intravesically administered gallium might be an effective therapy for bladder cancer, because its cytotoxicity is determined not by the amount of Tf receptor but by the gallium concentration and the duration of gallium exposure.