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.
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.
College of Laboratory Medicine, Medical University, Dalian, Liaoning Province, China.
Hongye
H
Ma
Department of Laparoscopic Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Lei
L
Cheng
Department of Nuclear Medicine, People's Hospital of Peking University, Beijing, China.
Keji
K
Hao
College of Laboratory Medicine, Medical University, Dalian, Liaoning Province, China.
Yanping
Y
Li
Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Xiaobo
X
Song
Department of Microbiology, Dalian Medical University, Dalian, Liaoning Province, China.
Huimin
H
Zhou
College of Laboratory Medicine, Medical University, Dalian, Liaoning Province, China.
Li
L
Jia
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D002648:Child; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D012799:Sialyltransferases; C513055:ABCB1 protein, human; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; C549032:ST6GAL2 protein, human; C421109:multidrug resistance-associated protein 1