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Journal of Ovarian Research

, 4:21

First Online: 05 December 2011Received: 12 October 2011Accepted: 05 December 2011

Abstract

BackgroundResistance to current chemotherapeutic agents is a major cause of therapy failure in ovarian cancer patients, but the exact mechanisms leading to the development of drug resistance remain unclear.

MethodsTo better understand mechanisms of drug resistance, and possibly identify novel targets for therapy, we generated a series of drug resistant ovarian cancer cell lines through repeated exposure to three chemotherapeutic drugs cisplatin, doxorubicin, or paclitaxel, and identified changes in gene expression patterns using Illumina whole-genome expression microarrays. Validation of selected genes was performed by RT-PCR and immunoblotting. Pathway enrichment analysis using the KEGG, GO, and Reactome databases was performed to identify pathways that may be important in each drug resistance phenotype.

ResultsA total of 845 genes p < 0.01 were found altered in at least one drug resistance phenotype when compared to the parental, drug sensitive cell line. Focusing on each resistance phenotype individually, we identified 460, 366, and 337 genes significantly altered in cells resistant to cisplatin, doxorubicin, and paclitaxel, respectively. Of the 845 genes found altered, only 62 genes were simultaneously altered in all three resistance phenotypes. Using pathway analysis, we found many pathways enriched for each resistance phenotype, but some dominant pathways emerged. The dominant pathways included signaling from the cell surface and cell movement for cisplatin resistance, proteasome regulation and steroid biosynthesis for doxorubicin resistance, and control of translation and oxidative stress for paclitaxel resistance.

ConclusionsOvarian cancer cells develop drug resistance through different pathways depending on the drug used in the generation of chemoresistance. A better understanding of these mechanisms may lead to the development of novel strategies to circumvent the problem of drug resistance.

Electronic supplementary materialThe online version of this article doi:10.1186-1757-2215-4-21 contains supplementary material, which is available to authorized users.

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Autor: Cheryl A Sherman-Baust - Kevin G Becker - William H Wood III - Yongqing Zhang - Patrice J Morin

Fuente: https://link.springer.com/







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