Effect of glucosylceramide synthase on P-gp expression by ERK signal transduction pathway in leukemia multi-drug resistance cell line.
- Author:
Yu-ling LI
1
;
Ke-ming XIE
;
Yang-yang ZHANG
;
Hui-jun MU
;
Bin ZHANG
;
Jian ZOU
;
Ping XIE
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; biosynthesis; genetics; metabolism; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glucosyltransferases; metabolism; Humans; K562 Cells; Leukemia; enzymology; genetics; metabolism; MAP Kinase Signaling System
- From: Chinese Journal of Medical Genetics 2012;29(3):270-274
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of glucosylceramide synthase (GCS) on P-glycoprotein (P-gp) expression via extracellular signal-regulated kinase (ERK) pathways in leukemia K562/A02 cell line.
METHODSK562/A02 multidrug resistance cells were treated with GCS siRNA and U0126, respectively. Expression of multidrug resistance protein 1 (MDR1) mRNA was analyzed with qRT-PCR. Phosphorylated ERK1/2, total ERK1/2 protein and P-gp in different groups were measured with Western blotting.
RESULTSAfter treated with U0126, P-ERK1/2 was decreased along with the increased U0126 concentration. P-ERK1/2 and P-gp were apparently down-regulated by U0126 at the concentrations of 20 μmol/L, 40 μmol/L and 60 μmol/L. After being transfected with GCS siRNA, GCS mRNA was inhibited by 70.50% (58.00%-76.00%) in K562/A02 cells. Compared with the negative control, both P-ERK1/2 and P-gp were inhibited significantly after RNAi for 72 hours (P<0.01 and P<0.05, respectively.
CONCLUSIONGCS may affect the expression of P-gp by ERK signal transduction pathway in leukemia cells.
