Abstract
β-galactoside α2, 6-sialyltransferse gene (ST6GAL) family has two members, which encode corresponding enzymes ST6Gal I and ST6Gal II. The present atudy was to investigate whether and how ST6GAL family involved in multidrug resistance (MDR) in human leukemia cell lines and bone marrow mononuclear cells (BMMC) of leukemia patients. Real-time PCR showed a high expression level of ST6GAL1 gene in both MDR cells and BMMCs (*P<0.05). Alternation of ST6GAL1 levels had a significant impact on drug-resistant phenotype changing of K562 and K562/ADR cells both in vitro and in vivo. However, no significant changes were observed of ST6GAL2 gene. Further data revealed that manipulation of ST6GAL1 modulated the activity of phosphoinositide 3 kinase (PI3K)/Akt signaling and consequently regulated the expression of P-glycoprotein (P-gp, *P<0.05) and multidrug resistance related protein 1 (MRP1, *P<0.05), which are both known to be associated with MDR. Therefore we postulate that ST6GAL1 is responsible for the development of MDR in human leukemia cells probably through medicating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1.
Highlights
multidrug resistance (MDR) and disease relapse are often regarded as the causes of the failure of chemotherapeutic drug treatments in patients diagnosed with malignant neoplasm including leukemia [1]
Our study continued to investigate the role of ST6GalI in mediating MDR in human leukemia cells and its possible mechanisms
We found the expression profiles of ST6GAL1 in four pairs of human leukemia cell lines and in the tumor cells of leukemia patients by using a real-time PCR analysis
Summary
MDR and disease relapse are often regarded as the causes of the failure of chemotherapeutic drug treatments in patients diagnosed with malignant neoplasm including leukemia [1]. ST6GalI is a sialyltransferase that links the sialic acid residues to terminal galactose of glycan chains by a- 2, 6-linkage [10]. It distributes widespread tissue-specific distribution in mammals, and the aberrant expression of ST6GalI is often related to poor prognoses in colon, epithelial tumors, gastric cancers and acute myeloid leukemia [6,11,12,13]. In contrast to ST6GalI, ST6GalII, a recently identified additional sialyltransferase, confines to human intestine, colon and brain [16,17] It exhibits relatively low and no activities toward some glycoproteins and glycolipids respectively and seems to recognize oligosaccharides to glycoproteins as acceptor substrates [18,19]. Tremendous studies have focused on the involvement of sialylation in tumorigenesis, but the relationship between ST6GalI or ST6GalII and MDR remains unclear
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