原创力文档the effect of vorinostat on the development of resistance to doxorubicin in neuroblastomavorinostat的影响在神经母细胞瘤耐阿霉素的发展.pdfVIP
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the effect of vorinostat on the development of resistance to doxorubicin in neuroblastomavorinostat的影响在神经母细胞瘤耐阿霉素的发展
The Effect of Vorinostat on the Development of
Resistance to Doxorubicin in Neuroblastoma
1,2 3 2 1,2 3 2
Timothy B. Lautz , Chunfa Jie , Sandra Clark , Jessica A. Naiditch , Nadereh Jafari , Yi-Yong Qiu ,
2 2 1,2
Xin Zheng , Fei Chu *, Mary Beth Madonna *
1 Department of Surgery, Lurie Children’s Hospital, Northwestern University, Chicago, Illinois, United States of America, 2 Cancer Biology Program, Children’s Memorial
Research Center, Northwestern University, Chicago, Illinois, United States of America, 3 Center for Genetic Medicine, Northwestern University, Chicago, Illinois, United
States of America
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
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