Study On Mechanisms Of GCS Inducing Multidrug Resistance By Affecting Apoptosis-related Genes In Leukemia Cells

Objective In order to explore the molecular mechanism of multidrug resistance induced by GCS, to study the modulation of GCS and affected apoptosis-related genes and protein by 1-phenyl-2-palmitoylamino-3-morpholino-1-propanal (PPMP) and GCS siRNA in human leukemia cell strain K562/AO2.Methods K562/AO2 cells were treated with PPMP and GCS siRNA, the differential expressions of GCS, Bcl-2 and Bax mRNA were analyzed by RT-PCR. Meanwhile, the expressions of Bcl-2 protein in different groups were measured by FCM.Results 1.The expressions of GCS gene and Bcl-2 gene and protein in K562/AO2 cells were higher than that in K562 cells significantly. 2. PPMP can obviously inhibit the expressions of GCS mRNA, and the genes and proteins of Bcl-2 were both down-regulated subsequently in K562/AO2 cells. 3.The expresson of GCS was sienced significantly by siRNA which is targeting GCS mRNA, and the expresson levels of Bcl-2 gene and protein were also decreased in K562/AO2 cells.4.The Bax mRNA expressions had no apparent change in different groups.Conclusion GCS gene may lead to multidrug resistance of human leukemia cells by Bcl-2 signal transduction.