Cancer letters, 2009-01, Vol.273 (1), p.70-79
2009
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- Autor(en) / Beteiligte
- Titel
- Combination of imatinib and vinorelbine enhances cell growth inhibition in breast cancer cells via PDGFR β signalling
- Ist Teil von
- Cancer letters, 2009-01, Vol.273 (1), p.70-79
- Ort / Verlag
- Ireland: Elsevier Ireland Ltd
- Erscheinungsjahr
- 2009
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- Abstract Introduction Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted against PDGFR α and β, c-kit and bcr-abl. These receptors regulate cellular processes such as proliferation, differentiation, and survival. This study was performed to evaluate the effects of imatinib on breast cancer cell lines with respect to the activity of PDGFR β and Akt: a downstream modulator of cell growth and survival. Methods Expression of imatinib targets was analyzed with reverse transciptase PCR and immunoblotting assays in the breast cell lines MDA MB 231, MCF 7, ZR 75-1, and T 47-D. Changes on receptor expression and phosphorylation status under imatinib were evaluated using drug concentrations of 2 to 10 μM. The anti-proliferative and pro-apoptotic effects of imatinib alone and in combination with vinorelbine were investigated with an MTT and TUNEL assay. Results Imatinib inhibited growth and induced apoptosis of all cell lines examined. This effect was increased when combined with vinorelbine. A dose-dependent inhibitory effect on the phosphorylation of PDGFR β and Akt was detected. Conclusions The growth inhibitory effect of imatinib on breast cell lines may be caused by inhibiting the activity of the tyrosine kinases PDGFR β and Akt. Imatinib is a promising novel drug for targeted therapy of breast cancer patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835eISSN: 1872-7980DOI: 10.1016/j.canlet.2008.07.040Titel-ID: cdi_proquest_miscellaneous_66726737
- Format
- –
- Schlagworte
- Akt, Antineoplastic Agents - pharmacology, Apoptosis, Benzamides, Breast cancer, Breast Neoplasms - metabolism, Breast Neoplasms - therapy, Cell Line, Tumor, Cell Proliferation - drug effects, Drug Therapy, Combination, Female, Hematology, Oncology and Palliative Medicine, Humans, Imatinib Mesylate, Immunoblotting, Immunohistochemistry, Oncogene Protein v-akt - metabolism, PDGFR, Phosphorylation - drug effects, Piperazines - pharmacology, Pyrimidines - pharmacology, Receptor, Platelet-Derived Growth Factor beta - drug effects, Receptor, Platelet-Derived Growth Factor beta - metabolism, Signal Transduction, Targeted therapy, Vinblastine - analogs & derivatives, Vinblastine - pharmacology