Key players of cisplatin resistance : towards a systems pharmacology approach

The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology app
The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell’s reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for relevant gene candidates. By combining statistical methods with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance. These and related genes were further validated on transcriptome (qRT-PCR) and proteome (Western blot) level to select candidates contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model of resistance-associated signalling alterations describing differential gene and protein expression between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.
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Metadaten
Author:Navin Sarin, Florian Engel, Florian Rothweiler, Jindrich Cinatl, Martin Michaelis, Roland Frötschl, Holger Fröhlich, Ganna V. Kalayda
URN:urn:nbn:de:hebis:30:3-458323
DOI:http://dx.doi.org/10.3390/ijms19030767
ISSN:1422-0067
ISSN: 1661-6596
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=29518977
Parent Title (English):International journal of molecular sciences
Publisher:Molecular Diversity Preservation International
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/03/07
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/03/15
Tag:CCL2; DOK1; HRas; JNK3; PTK2B; cellular signalling; cisplatin resistance; p38
Volume:19
Issue:3, Art. 767
Pagenumber:18
First Page:1
Last Page:18
Note:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
HeBIS PPN:432321810
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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