Effect of glucosylceramide synthase on P-gp expression by ERK signal transduction pathway in leukemia multi-drug resistance cell line].

Yu-ling Li, Ke-ming Xie, Yang-yang Zhang, Hui-jun Mu, Bin Zhang, Jian Zou, Ping Xie

Department of Pathophysiology, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China.

Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 2012 Jun

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To 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. K562/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. After 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. GCS may affect the expression of P-gp by ERK signal transduction pathway in leukemia cells.)

Citation

Yu-ling Li, Ke-ming Xie, Yang-yang Zhang, Hui-jun Mu, Bin Zhang, Jian Zou, Ping Xie. Effect of glucosylceramide synthase on P-gp expression by ERK signal transduction pathway in leukemia multi-drug resistance cell line]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2012 Jun;29(3):270-4