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.
Hata
Y
Y
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
Sandler
A
A
Loehrer
P J
PJ
Sledge
G W
GW
Weber
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005708:Gallium / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D014411:Neoplastic Stem Cells / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D005708:Gallium; D017239:Paclitaxel; C027235:gallium nitrate