B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line

被引：25
作者：
Zhou, Huimin [1 ,2 ]
Zhang, Zhaohai [1 ]
Liu, Chunqing [1 ]
Jin, Changgong [3 ]
Zhang, Jianing [4 ]
Miao, Xiaoyan [1 ]
Jia, Li [1 ]
机构：
[1] Dalian Med Univ, Coll Lab Med, Dept Lab Med, Dalian 116044, Liaoning Provin, Peoples R China
[2] Dalian Med Univ, Dept Microbiol, Dalian 116044, Liaoning Provin, Peoples R China
[3] Dalian Med Univ, Dept State Owned Property Management, Dalian 116044, Liaoning Provin, Peoples R China
[4] Dalian Med Univ, Dept Biochem, Dalian 116044, Liaoning Provin, Peoples R China
来源：
IUBMB LIFE | 2012年 / 64卷 / 11期
基金：
中国国家自然科学基金;
关键词：
B4GALT1; glycogene; multidrug resistance; human leukemia cell line; hedgehog; DRUG-RESISTANCE; BETA-1,4-GALACTOSYLTRANSFERASE I; SONIC HEDGEHOG; BREAST-CANCER; STEM-CELLS; EXPRESSION; IDENTIFICATION; GLYCOSYLATION; INFLAMMATION; MECHANISMS;
D O I：
10.1002/iub.1080
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
B4GALT1 gene encodes type II membrane-bound glycoprotein, named beta-1, 4-galactosyltransferase 1 (beta 1, 4-Gal-T1), which can transfer galactose to acceptor sugars. B4GALT1 gene plays important roles in physiological process and disease development. In this study, we investigate the possible role and mechanism of B4GALT1 gene in multidrug resistance of human leukemia cell line. Significantly, higher expression of B4GALT1 was observed in adriamycin-resistant (ADR) K562 cell line (K562/ADR) than that in K562 cell line by real-time polymerase chain reaction and Western blotting. The activity of beta 1, 4-Gal-T1 enzyme, and Gal beta-1,4GlcNAc structures on cell membrane glycoproteins was found at higher levels in K562/ADR cells than those in K562 cells. Further analysis of the B4GALT1 deregulation after using RNA interference approach showed that the silencing of B4GALT1 in K562/ADR cells resulted in increased sensitivity to chemotherapeutic drugs both in vitro and in vivo. The activity of the hedgehog signaling pathway affected the chemosensitivity of K562/ADR cells and was downregulated in K562/ADR cells with suppression of B4GALT1 gene. We hypothesize that B4GALT1 is responsible for the overcoming multidrug resistance in human leukemia therapy via regulating the activity of the hedgehog signaling pathway. (c) 2012 IUBMB, IUBMB Life, 64(11): 889900, 2012
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页码：889 / 900
页数：12
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