Abstract:
Objective To investigate the effect of secreted frizzled-related protein 5(SFRP5) on leukemic multidrug resistance.
Methods Transgenic methods were used to culture KG1a cells expressing SFRP5 and enhanced green fluorescent protein(control).mdr1 mRNA expression in KG1a, KG1a/eGFP, and KG1a/SFRP5 groups were detected by real-time polymerase chain reaction.P-glycoprotein(P-gp) expression was detected by Western blot analysis.P-gp expression on the cell surface was observed by immunofluorescence.Intracellular drug concentration was detected by flow cytometry.Drug resistance was detected by MTT assay.
Results The KG1a/SFRP5 cell, a KG1a cell expressing SFRP5, and the KG1a/eGFP cell, a KG1a cell expressing eGFP, were successfully constructed.The multidrug resistance protein 1(mdr1) mRNA level in KG1a/SFRP5 cells was significantly decreased(P < 0.01).P-gp expression in KG1a/SFRP5 cells was also downregulated.Fluorescence intensity of P-gp on the KG1a/SFRP5 cell surface was reduced.Rhodamine concentration in KG1a/ SFRP5 cell was significantly increased(P < 0.01).IC50of KG1a/SFRP5 cell to Adriamycin was decreased as determined by the MTT method.
Conclusion SFRP5 expression in KG1a cells can downregulate MDR1 transcription and P-gp expression, increase intracellular drug concentration, and reverse multidrug resistance.