title: The effect of vorinostat on the development of resistance to doxorubicin in neuroblastoma.
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.
authors: Department of Surgery, Lurie Children's Hospital, Northwestern University, Chicago, Illinois, USA.
authors: Timothy B
authors: TB
authors: Lautz
authors: Chunfa
authors: C
authors: Jie
authors: Sandra
authors: S
authors: Clark
authors: Jessica A
authors: JA
authors: Naiditch
authors: Nadereh
authors: N
authors: Jafari
authors: Yi-Yong
authors: YY
authors: Qiu
authors: Xin
authors: X
authors: Zheng
authors: Fei
authors: F
authors: Chu
authors: Mary Beth
authors: MB
authors: Madonna
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D000077337:Vorinostat; D004317:Doxorubicin