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

Oncol Res. 1994;6(1):19-24.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Drug Administration Schedule
  • Drug Synergism
  • Gallium / administration & dosage*
  • Gallium / pharmacology
  • Humans
  • Kinetics
  • Neoplastic Stem Cells / drug effects
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacology
  • Tumor Cells, Cultured

Substances

  • Gallium
  • Paclitaxel
  • gallium nitrate