Glucosylceramide synthase upregulates apoptosis-related gene bcl-2 ex-pression via MEK/ERK signaling pathway in leukemia multidrug-resis-tant cell line
- VernacularTitle:GCS 通过 MEK／ERK 通路调控白血病多药耐药细胞凋亡相关基因 bcl-2的表达
- Author:
Qian WANG
;
Jian ZOU
;
Xiufen ZHANG
;
Huijun MU
;
Ying YIN
;
Ping XIE
- Publication Type:Journal Article
- Keywords:
Glucosylceramide synthase;
MEK/ERK signaling pathway;
Genes,bcl-2;
Drug resistance,multiple
- From:
Chinese Journal of Pathophysiology
2015;(1):114-118
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate whether glucosylceramide synthase (GCS) regulates apoptosis-related gene bcl-2 expression via MEK/ERK signaling pathway , thus enhancing drug resistance of K 562/A02 human leukemia multidrug resistant cell line.METHODS:siRNA targeting GCS was transfected into K562/A02 cells.Bcl-2, p-ERK and total ERK expression at mRNA and protein levels after GCS knockdown were detected by real-time PCR and Western blotting .After exposed to MEK-ERK pathway inhibitor U0126, the expression of Bcl-2 at mRNA and protein levels also was analyzed by real-time PCR and Western blotting , respectively.The viability of the cells was evaluated by CCK-8 assay.RESULTS:The expression of GCS and Bcl-2, as well as MEK/ERK signaling were significantly inhibited in K 562/A02 cells by GCS siRNA transfection compared with negative control group .Inactivation of MEK/ERK signaling due to U0126 treatment de-creased Bcl-2 mRNA and protein levels in a concentration-dependent manner , and sensitized K562/A02 cells to adriamy-cin.CONCLUSION:GCS may affect the expression of apoptosis-related gene bcl-2 by MEK/ERK signaling pathway , thus regulating multidrug resistance of human leukemia K 562/A02 cells.
