INTRODUCTION: Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted against PDGFR alpha and beta, 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 beta 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 microM. 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 beta 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 beta and Akt. Imatinib is a promising novel drug for targeted therapy of breast cancer patients.
INTRODUCTION:Imatinib mesylate is a tyrosine kinase receptor inhibitor targeted against PDGFR alpha and beta, 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 beta 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 microM. 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 beta 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 beta and Akt. Imatinib is a promising novel drug for targeted therapy of breast cancerpatients.
Authors: Marion T Weigel; Linda Dahmke; Christian Schem; Dirk O Bauerschlag; Katrin Weber; Peter Niehoff; Maret Bauer; Alexander Strauss; Walter Jonat; Nicolai Maass; Christoph Mundhenke Journal: BMC Cancer Date: 2010-08-09 Impact factor: 4.430
Authors: Clinton Yam; Rashmi K Murthy; Gaiane M Rauch; James L Murray; Ronald S Walters; Vicente Valero; Abenaa M Brewster; Robert C Bast; Daniel J Booser; Sharon H Giordano; Francisco J Esteva; Wei Yang; Gabriel N Hortobagyi; Stacy L Moulder; Banu Arun Journal: Invest New Drugs Date: 2018-10-11 Impact factor: 3.651