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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 654291, 8 pages
http://dx.doi.org/10.1155/2012/654291
Research Article

Analyzing Gene Expression Profile in K562 Cells Exposed to Sodium Valproate Using Microarray Combined with the Connectivity Map Database

1Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong 510630, Guangzhou, China
2Prenatal Diagnosis Center, The Women and Children Hospital of Guangdong Province, Guangdong 510010, Guangzhou, China
3Key Laboratory of Department of Health of Guangdong Province for Maternal and Children Metabolic-Genetic Disease Diagnosis, Guangdong 510010, Guangzhou, China
4Department of Hematology, First Affiliated Hospital of Sun Yat-sen University, Guangdong 510080, Guangzhou, China
5Department of Hematology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Anhui 230001, Hefei, China
6Department of Hematology, Guizhou Provincial Hospital, Guizhou 550002, Guiyang, China

Received 6 February 2012; Revised 26 March 2012; Accepted 9 April 2012

Academic Editor: Eric W. Lam

Copyright © 2012 Xiang-Zhong Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

To explore the mechanism underlying antileukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed and validated. The differentially expressed genes identified were further used to query the connectivity map database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis and a change in gene expression profile were observed in valproate-exposed K562 cells. The significant enrichment analysis of gene ontology terms for the differentially expressed genes showed that these genes were involved in many important biological processes. Eight differentially expressed genes involved in apoptosis were verified by quantitative real-time PCR. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate was most similar to that of HDACi and PI3K inhibitors, suggesting that sodium valproate might exert antileukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, our data might provide clues to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment, and the connectivity map is a useful tool for exploring the molecular mechanism of drug action.