Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines
Joint Authors
Lange, Falko
Franz, Benjamin
Hühns, Maja
Jaster, Robert
Maletzki, Claudia
Linnebacher, Michael
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-09-17
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Low-passage cancer cell lines are versatile tools to study tumor cell biology.
Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC) patients, to evaluate effects of the small molecule kinase inhibitors (SMI) vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting.
The mutant BRAF (V600E/V600K) inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only.
In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant.
The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations.
Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling.
In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI.
Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.
American Psychological Association (APA)
Lange, Falko& Franz, Benjamin& Maletzki, Claudia& Linnebacher, Michael& Hühns, Maja& Jaster, Robert. 2014. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines. BioMed Research International،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1034500
Modern Language Association (MLA)
Lange, Falko…[et al.]. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines. BioMed Research International No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-1034500
American Medical Association (AMA)
Lange, Falko& Franz, Benjamin& Maletzki, Claudia& Linnebacher, Michael& Hühns, Maja& Jaster, Robert. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-1034500
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1034500