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Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach

Sarin, Navin, Engel, Florian, Rothweiler, Florian, Cinatl, Jindrich, Michaelis, Martin, Frötschl, Roland, Fröhlich, Holger, Kalayda, Ganna V (2018) Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach. International Journal of Molecular Sciences, 19 (3). pp. 767-785. ISSN 1422-0067. (doi:10.3390/ijms19030767)

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https://doi.org/10.3390/ijms19030767

Abstract

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.

Item Type: Article
DOI/Identification number: 10.3390/ijms19030767
Uncontrolled keywords: cisplatin resistance; cellular signalling; HRas; p38; CCL2; DOK1; PTK2B; JNK3
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Martin Michaelis
Date Deposited: 11 Apr 2018 14:16 UTC
Last Modified: 29 May 2019 20:27 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/66690 (The current URI for this page, for reference purposes)
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
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