NF-κ B mediates the effect of glucosylceramide synthase on P-glycoprotein modulation in a drug-resistance leukemia cell line

• Published in: Zhonghua yi xue yi chuan xue za zhi Vol. 31; no. 1; p. 34
• Main Authors: Zhang, Xiufen, Xie, Keming, Zou, Jian, Li, Yuling, Mu, Huijun, Zhang, Bin, Xie, Ping
• Format: Journal Article
• Language: Chinese
• Published: China 01.02.2014
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glucosyltransferases - genetics; Glucosyltransferases - metabolism; Humans; K562 Cells; Leukemia - genetics; NF-kappa B - genetics; NF-kappa B - metabolism
• ISSN: 1003-9406
• DOI: 10.3760/cma.j.issn.1003-9406.2014.01.008

To investigate whether transcription factor-kappaB (NF-κ B) is involved in the modulation of P-glycoprotein (P-gp) by glucosylceramide synthase (GCS) in a multidrug resistance leukemia cell line K562/A02 and to explore the relationship between NF-κ B and extracelluar signal-regulated kinase (ERK). K562/A02 cells were treated with GCSsiRNA, pyrrolidine dithiocarbamate (PDTC, a NF-κ B specific inhibitor) and U0126 (a MEK1/2 inhibitor), respectively. The expression of GCS and multidrug resistance protein 1 (MDR1) mRNA were analyzed with qRT-PCR. Various proteins of different groups were measured by Western blotting. After transfected with GCSsiRNA for 48 h, GCS mRNA were reduced by 62% (51%-73%) and MDR1 mRNA was reduced by 52% (43%-61%) in the K562/A02 cells. Compared with the negative control, relative expression of NF-κ B p65 in nuclear and P-ERK1/2 were both down-regulated, and P-gp was also inhibited significantly at 72 h after transfected with GCSsiRNA (P< 0.05). In addition, the expression of P-gp was dec