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《Chinese Journal of Pathophysiology》 2015-01
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Glucosylceramide synthase upregulates apoptosis-related gene bcl-2 expression via MEK/ERK signaling pathway in leukemia multidrug-resistant cell line

WANG Qian;ZOU Jian;ZHANG Xiu-fen;MU Hui-jun;YIN Ying;XIE Ping;Central Laboratory,The Affiliated Wuxi People's Hospital,Nanjing Medical University;  
AIM: To investigate whether glucosylceramide synthase( GCS) regulates apoptosis-related gene bcl-2 expression via MEK / ERK signaling pathway,thus enhancing drug resistance of K562 / 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 K562 / A02 cells by GCS siRNA transfection compared with negative control group. Inactivation of MEK / ERK signaling due to U0126 treatment decreased Bcl-2 mRNA and protein levels in a concentration-dependent manner,and sensitized K562 / A02 cells to adriamycin. CONCLUSION: GCS may affect the expression of apoptosis-related gene bcl-2 by MEK / ERK signaling pathway,thus regulating multidrug resistance of human leukemia K562 / A02 cells.
【Fund】: 无锡市科技发展指令性计划(No.CSEY1N1101)
【CateGory Index】: R733.7
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