title: Decreased response to paclitaxel versus docetaxel in HER-2/neu transfected human breast cancer cells.
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.
authors.affiliation: Departments of Medicine, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.
authors.forename: Lois M
authors.initials: LM
authors.lastname: Witters
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Santala
authors.forename: Linda
authors.initials: L
authors.lastname: Engle
authors.forename: Vernon
authors.initials: V
authors.lastname: Chinchilli
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel