Effect of a combination of tyrosine kinase inhibitor imatinib with doxorubicin shows in breast cancer cell lines.

Abstract

e13657 Background: In the need to optimize breast cancer therapies, constantly new targeted agents are examined for their potential clinical use. In a broad range of solid and haematological cancers tyrosine kinase inhibitors, which target growth factor receptors like PDGFR α and β as well as c-kit, have already shown to be of clinical benefit with tolerable side effects. Here effects of the tyrosine kinase inhibitor imatinib as a single agent and in combination with standard chemotherapy (doxorubicin) have been investigated in vitro. Methods: Biological effects of imatinib in breast cancer cell lines MDAMB 231 and MCF 7 were tested using proliferation assays, TUNEL assays and migration assays. Cells were incubated with different concentrations of doxorubicin (0,25 nmol-500μmol) and imatinib (1-15 μmol) each as single agent and in combination. Results: Incubation with imatinib as a single agent reduces cell proliferation in a dose-dependent manner with an IC 50 of 6uM for both breast cancer cell lines. Moreover, imatinib induces apoptosis and reduces cell migration. Combining imatinib with doxorubicin leads to an additive effect on cell growth inhibition in MDA MB 231 and MCF 7 cells. A further reduction in cell migration can be detected when imatinib is combined with doxorubicin. In the hormone receptor positive cell line MCF 7, a significant increase in apoptotic cells can be detected when combining both drugs compared to each single treatment. The concentrations of doxorubicin as well as the imatinib concentrations can be applied in clinical use. Conclusions: Combining imatinib with doxorubicin shows a significant improvement in inhibiting breast cancer cell proliferation and migration, as well as apoptosis induction. These data suggest that the combination of standard chemotherapy with imatinib could be beneficial for breast cancer patients. No significant financial relationships to disclose.