Analyzing gene expression profile in K562 cells exposed to sodium valproate using microarray combined with the connectivity map database.
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.
Department of Hematology, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong 510630, Guangzhou, China.
Xiang-Zhong
XZ
Zhang
Ai-Hua
AH
Yin
Dong-Jun
DJ
Lin
Xiao-Yu
XY
Zhu
Qian
Q
Ding
Chun-Huai
CH
Wang
Yun-Xian
YX
Chen
D017209:Apoptosis / Q000187:drug effects*; D016208:Databases, Factual; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D059467:Transcriptome; D014635:Valproic Acid / Q000008:administration & dosage*
D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014635:Valproic Acid