title: [NF-κ B mediates the effect of glucosylceramide synthase on P-glycoprotein modulation in a drug-resistance leukemia cell line].
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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 decreased at 24 h with 80 μ mol/L PDTC and 48 h with 20 μ mol/L PDTC. P-ERK1/2 was inhibited significantly when the cells were treated with 20 μ mol/L U0126 for 48 h. The expression of NF-κ B p65 in nuclear and P-gp were also down-regulated.
  
  
  CONCLUSIONS
  NF-κ B can modulate the effect of GCS on P-gp in K562/A02 cells. P-ERK1/2 can activate NF-κ B in above signal transduction pathway.
authors: Department of Pathophysiology, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R.China. xieping1115@163.com.
authors: Xiufen
authors: X
authors: Zhang
authors: Keming
authors: K
authors: Xie
authors: Jian
authors: J
authors: Zou
authors: Yuling
authors: Y
authors: Li
authors: Huijun
authors: H
authors: Mu
authors: Bin
authors: B
authors: Zhang
authors: Ping
authors: P
authors: Xie
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005964:Glucosyltransferases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016328:NF-kappa B; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase