Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells

Am J Clin Oncol. 2003 Feb;26(1):50-4. doi: 10.1097/00000421-200302000-00011.

Abstract

Taxanes are effective in the treatment of metastatic breast cancer. Docetaxel has been shown to be more potent than paclitaxel in inducing bcl-2 phosphorylation and apoptosis and is clinically active in some paclitaxel-resistant breast tumors. HER-2/neu overexpression has been shown to correlate with resistance to hormonal therapy as well as chemotherapy. Using a HER-2/neu transfected MCF-7 human breast cancer cell line, we investigated the role of HER-2/neu overexpression on resistance to paclitaxel and docetaxel treatment. A control vector transfected MCF-7 human breast cancer cell line (MCF/neo) and a HER-2/neu transfected MCF-7 line (MCF/18) were treated with various concentrations of docetaxel or paclitaxel. Cell number was assessed using the MTT tetrazolium dye assay. In the control vector transfected MCF/neo cell line, paclitaxel and docetaxel gave similar dose-dependent growth inhibition ( p = 0.175). In HER-2/neu transfected MCF/18 cells, docetaxel treatment resulted in a dose-dependent inhibition similar to that seen in MCF/neo cells. Paclitaxel, however, gave significantly less growth inhibition than docetaxel in the HER-2/neu overexpressing MCF/18 cells (p = 0.0003). These data suggest that HER-2/neu overexpression may contribute to paclitaxel resistance. In contrast, the cytotoxic effects of docetaxel in these breast carcinoma cells are not affected by HER-2/neu expression. Therefore, docetaxel may be the preferred taxane therapy in HER-2/neu overexpressing breast tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Cell Division / drug effects
  • Cell Division / genetics
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • Drug Screening Assays, Antitumor
  • Gene Expression
  • Genes, erbB-2 / genetics*
  • Humans
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology*
  • Taxoids*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Phytogenic
  • Taxoids
  • Docetaxel
  • Paclitaxel