Synergism of taxol and gallium nitrate in human breast carcinoma cells: schedule dependency.

Since Taxol (paclitaxel, NSC-125973) arrests cells in mitosis and gallium nitrate (NSC-15200) inhibits cell replication in the S phase, and the two drugs have different biochemical targets, we tested the hypothesis that the combination of these drugs may be synergistic in human breast carcinoma cells. MDA-MB-435 human breast carcinoma cells were grown in monolayer in culture. Taxol and gallium inhibited cell proliferation with IC50 = 13 nM and 180 microM, respectively. In clonogenic assays, Taxol and gallium yielded IC50 = 2 nM and 25 microM, respectively. Synergism was observed in both cell proliferation and colony formation assays depending on the treatment schedule. Gallium (300 microM) 24 h prior to Taxol (10 nM) synergistically decreased cell proliferation to 6.5% of untreated cells, which was 50% of the predicted value. In clonogenic assay, gallium (40 microM) given 16 h prior to Taxol (2 nM) yielded 8.7% colony formation of the untreated cells, which was 44% of the predicted value. Combination chemotherapy with Taxol and gallium with this protocol schedule may be useful in the treatment of human breast carcinoma.