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The effect of vorinostat on the development of resistance to doxorubicin in neuroblastoma
- Source :
- PLoS ONE, Vol 7, Iss 7, p e40816 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Histone deacetylase (HDAC) inhibitors, especially vorinostat, are currently under investigation as potential adjuncts in the treatment of neuroblastoma. The effect of vorinostat co-treatment on the development of resistance to other chemotherapeutic agents is unknown. In the present study, we treated two human neuroblastoma cell lines [SK-N-SH and SK-N-Be(2)C] with progressively increasing doses of doxorubicin under two conditions: with and without vorinsotat co-therapy. The resultant doxorubicin-resistant (DoxR) and vorinostat-treated doxorubicin resistant (DoxR-v) cells were equally resistant to doxorubicin despite significantly lower P-glycoprotein expression in the DoxR-v cells. Whole genome analysis was performed using the Ilumina Human HT-12 v4 Expression Beadchip to identify genes with differential expression unique to the DoxR-v cells. We uncovered a number of genes whose differential expression in the DoxR-v cells might contribute to their resistant phenotype, including hypoxia inducible factor-2. Finally, we used Gene Ontology to categorize the biological functions of the differentially expressed genes unique to the DoxR-v cells and found that genes involved in cellular metabolism were especially affected.
- Subjects :
- Cancer Treatment
Gene Expression
lcsh:Medicine
Antineoplastic Agents
Biology
Hydroxamic Acids
Epigenetic Therapy
Adrenal Tumors
Neuroblastoma
Cell Line, Tumor
Molecular Cell Biology
Basic Cancer Research
Gene expression
Genetics
medicine
Humans
Doxorubicin
Endocrine Tumors
lcsh:Science
Vorinostat
Gene
Regulation of gene expression
Multidisciplinary
lcsh:R
Cancers and Neoplasms
Histone Modification
Chemotherapy and Drug Treatment
medicine.disease
Molecular biology
Gene Expression Regulation, Neoplastic
Oncology
Drug Resistance, Neoplasm
Pediatric Oncology
Cell culture
Medicine
Epigenetics
lcsh:Q
Histone deacetylase
Research Article
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....618bf013ff6f2e785c9682458a603799