AI Article Synopsis
- The study aimed to explore how glucosylceramide synthase (GCS) influences the expression of P-glycoprotein (P-gp) through ERK signaling pathways in leukemia cells (K562/A02).
- Researchers treated the cells with GCS siRNA and U0126 to analyze the impact on MDR1 mRNA levels and protein expression of P-gp and ERK using qRT-PCR and Western blotting.
- Results showed that inhibiting GCS and using U0126 led to a significant decrease in both P-ERK1/2 and P-gp levels, suggesting that GCS plays a role in modulating P-gp expression via the ERK pathway in leukemia cells.
Article Abstract
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: GCS may affect the expression of P-gp by ERK signal transduction pathway in leukemia cells.
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| http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2012.03.005 | DOI Listing |
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