Next Article in Journal
ATG-18 and EPG-6 are Both Required for Autophagy but Differentially Contribute to Lifespan Control in Caenorhabditis elegans
Previous Article in Journal
Selected Aspects of Chemoresistance Mechanisms in Colorectal Carcinoma—A Focus on Epithelial-to-Mesenchymal Transition, Autophagy, and Apoptosis
Open AccessArticle

Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells

Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic
Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic
Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 753/5, CZ-625 00 Brno, Czech Republic
Author to whom correspondence should be addressed.
Cells 2019, 8(3), 235;
Received: 15 February 2019 / Revised: 6 March 2019 / Accepted: 8 March 2019 / Published: 12 March 2019
(This article belongs to the Section Cell Nuclei: Function, Transport and Receptors)
The efficiency of cisplatin (CDDP) is significantly hindered by the development of resistance during the treatment course. To gain a detailed understanding of the molecular mechanisms underlying the development of cisplatin resistance, we comparatively analyzed established a CDDP-resistant neuroblastoma cell line (UKF-NB-4CDDP) and its susceptible parental cells (UKF-NB-4). We verified increased chemoresistance of UKF-NB-4CDDP cells by analyzing the viability, induction of apoptosis and clonal efficiency. To shed more light on this phenomenon, we employed custom cDNA microarray (containing 2234 probes) to perform parallel transcriptomic profiling of RNA and identified that 139 genes were significantly up-regulated due to CDDP chemoresistance. The analyses of molecular pathways indicated that the top up-regulation scoring functions were response to stress, abiotic stimulus, regulation of metabolic process, apoptotic processes, regulation of cell proliferation, DNA repair or regulation of catalytic activity, which was also evidenced by analysis of molecular functions revealing up-regulation of genes encoding several proteins with a wide-spectrum of enzymatic activities. Functional analysis using lysosomotropic agents chloroquine and bafilomycin A1 validated their potential to re-sensitize UKF-NB-4CDDP cells to CDDP. Taken together, the identification of alterations in specific genes and pathways that contribute to CDDP chemoresistance may potentially lead to a renewed interest in the development of novel rational therapeutics and prognostic biomarkers for the management of CDDP-resistant neuroblastoma. View Full-Text
Keywords: neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport neuroblastoma; cisplatin; chemoresistance; microarray; lysosomes; transport
Show Figures

Figure 1

MDPI and ACS Style

Rodrigo, M.A.M.; Buchtelova, H.; Jimenez, A.M.J.; Adam, P.; Babula, P.; Heger, Z.; Adam, V. Transcriptomic Landscape of Cisplatin-Resistant Neuroblastoma Cells. Cells 2019, 8, 235.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop