Skip to main content

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) (KAR id:66690)

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: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 11 Apr 2018 14:16 UTC
Last Modified: 08 Dec 2022 21:35 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/66690 (The current URI for this page, for reference purposes)

University of Kent Author Information

  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.