[Relation between glucosylceramide synthase and multidrug resistance in leukemia cells].
This study was purposed to explore the expression of glucosylceramide synthase (GCS) in human leukemia cells and its relationship with multidrug resistance. RT-PCR was used to analyze peripheral blood samples from 53 leukemia patients with multidrug resistance/non-resistance, and to detect the expression level of GCS gene in HL-60 cells and HL-60/ADR cells, the expression level was compared with the level of mdr-1. The expressions of GCS protein and P-gp protein in HL-60 cells and HL-60/ADR cells were assayed by Western blot analysis. The results showed that the relative optical density ratio of GCS gene amplified bands in samples of leukemia patients with drug-resistance was significantly higher than that in samples of leukemia patients with drug non-resistance group (P < 0.05), meanwhile the significant enhancement of optical density value of GCS gene amplified bands accompanied by high expression of mdr-1 gene. Their correlation showed positive (P < 0.01, r = 0.6). The GCS mRNA and protein were overexpressed in HL-60/ADR cells, and their expression levels were obviously higher than that in HL-60 cells, meanwhile the expression of mdr-1 mRNA and P-gp also significantly increased in HL-60/ADR cells. It is concluded that the high level of GCS in leukemia patients possibly is associated with multidrug resistance of leukemia cells.
Xie
Ping
P
Centrol Laboratory, The First Affiliated Hospital of Wuxi, Nanjing Medical University, Wuxi 214002, China. xieping1115@163.com
Ge
Shu-Mei
SM
Sheng
Yun-Feng
YF
Gu
Zhong-Hua
ZH
Mu
Hui-Jun
HJ
Zhang
Bin
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005964:Glucosyltransferases / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D004317:Doxorubicin; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase