title: α-2,8-Sialyltransferase Is Involved in the Development of Multidrug Resistance via PI3K/Akt Pathway in Human Chronic Myeloid Leukemia.
abstract: Cell surface sialylation is emerging as an important feature of cancer cell multidrug resistance (MDR). We have focused on the influence of 2,8-sialyltransferases in key steps of the development of MDR in chronic myeloid leukemia (CML). The expressional profiles of six α-2,8-sialyltransferases were generated in three pairs of CML cell lines and peripheral blood mononuclear cells (PBMC) of CML patients. Cellular MDR phenotype positively correlated with ST8SIA4 and ST8SIA6 levels. Furthermore, ST8SIA4 mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signal pathway and the expression of P-glycoprotein (P-gp). Targeting the PI3K/Akt pathway by its specific inhibitor LY294002, or by Akt RNA interfering reversed the MDR phenotype of K562/ADR cells. Inhibition of PI3K/Akt pathway also attenuated the effects caused by the overexpression of ST8SIA4 on MDR. Therefore this study indicated that α-2,8-sialyltransferases involved in the development of MDR of CML cells probably through ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp.
authors: Department of Medical Laboratory, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning Province, China.
authors: Xu
authors: X
authors: Zhang
authors: Weijie
authors: W
authors: Dong
authors: Huimin
authors: H
authors: Zhou
authors: Hongshuai
authors: H
authors: Li
authors: Ning
authors: N
authors: Wang
authors: Xiaoyan
authors: X
authors: Miao
authors: Li
authors: L
authors: Jia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D012799:Sialyltransferases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C515117:ST8SIA4 protein, human; C000607061:ST8SIA6 protein, human
keywords: PI3K/Akt signal pathway; human leukemia cell line; multidrug resistance; α-2,8-sialyltransferases