PloS one · 2014
Reversal effect of ST6GAL 1 on multidrug resistance in human leukemia by regulating the PI3K/Akt pathway and the expression of P-gp and MRP1.
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Ma Hongye, Cheng Lei, Hao Keji, Li Yanping, Song Xiaobo, Zhou Huimin, Jia Li
Аннотация
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.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1AdolescentAdultAgedAntigens, CDChildDrug Resistance, MultipleDrug Resistance, NeoplasmFemaleGene ExpressionGene Expression Regulation, LeukemicGene Knockdown TechniquesHumansK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, Myeloid, AcuteMaleMiddle AgedATP-Binding Cassette, Sub-Family C ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, Small InterferingSialyltransferasesYoung Adultbeta-D-Galactoside alpha 2-6-Sialyltransferase