Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance
Received 17 October 2017
Accepted for publication 22 November 2017
Published 4 January 2018 Volume 2018:11 Pages 221—237
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Carlos E Vigil
Anna Vert1,2 Jessica Castro,1,2 Marc Ribó,1,2 Maria Vilanova,1,2 Antoni Benito1,2
1Protein Engineering Laboratory, Department of Biology, Faculty of Sciences, Universitat de Girona, 2Biomedical Research Institute of Girona (IDIBGi), Girona, Spain
Background: Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance.
Methods: NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8.
Results: Gene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK–Akt, Wnt, and Notch.
Conclusion: Our findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs.
Keywords: multidrug resistance, microarray analysis, ovarian cancer, drug extrusion, drug inactivation
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