The effects of various combinations of different classes of anticancer drugs and tyrosine kinase inhibitors on the human MCF-7 breast carcinoma cell line

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Date

2014

Journal Title

Journal ISSN

Volume Title

Publisher

University of the Western Cape

Abstract

This study investigated the effects of TKIs on the growth and proliferation of MCF-7 breast carcinoma cells in culture. MCF-7 cells were exposed to different concentrations of TKIs alone and in combination with each other. Inhibition of cell growth by TKIs used individually occurred in a dose- and time-dependent manner. When EGFR Inhibitor I, EGFR Inhibitor II/BIBX1382 and the multi-specific EGFR/ErbB-2/ErB-4 Inhibitor were used in combination with each other at equimolar log dose concentrations, the combined effects on cell growth was significantly different to inhibitors used individually as reflected in a decreased EC50 (IC50) during combination treatments. Generally, for the combinations with DOX, CPL and the TKIs, synergistic as well as antagonistic effects were observed at isoeffective concentrations with resultant decreases in dose reduction indices (DRIs) implying greater efficacies with the respective combinations. In this study, conventional PCR was used to detect and illustrate the presence of the EGFR gene in the samples, while RT-qPCR was used to determine the mRNA expression levels of this gene in MCF-7 breast carcinoma cells

Description

Magister Scientiae (Medical Bioscience) - MSc(MBS)

Keywords

Breast cancer, Human MCF-7 breast carcinoma cells, Epidermal growth factor receptor, Tyrosine kinase inhibitors, Doxorubicin, Cisplatin, EGFR inhibitor I, EGFR inhibitor II/BIBX1382, EGFR/ErbB2/ErbB4 inhibitor, Dose-response curves, IC50/EC50, Drug combination analysis, Synergism, Antagonism, Dose-reduction indices, Haematoxylin and eosin staining, Annexin V-Cy3 fluorescent staining, Apoptosis, EGFR gene expression analysis, Real-time qPCR

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