To explore the effect of NF-κB on bcl-x gene transcription in extended drug resistance leukemia cell line HL-60/E6, drug-resistant subline HL-60/E6 was derived by intermittently exposing HL-60 cells to 6 ng/ml epirubicin. Indirect immunofluorescence was used to demonstrate the location of NF-κB-RelA in HL-60/E6 cells. FCM analysis and RT-PCR were used to detect the efficiency of liposome-mediated ODN transfection and the change of bcl-x L mRNA levels after 5 μmol/L phosphorothioate (PS)-derivatized antisense (AS) oligodeoxynucleotide (ODN) directed to RelA was transferred into HL-60/E6 cells. The results showed that RelA remained persistently active and located at the nuclei of HL-60/E6 cells, but in the cytoplasm of HL-60 cells, the efficiency of liposomemediated ODN transfection was significantly higher than that of null ODN (P<0. 01 in 4 h, 6 h, 12 h, 24 h). Exposure of HL-60/E6 cells to 5 μmol/L AS-PS-ODN directed to RelA led to a maximal 40% decline of bcl-x L mRNA levels within 8 h. The inhibition rate of bcl-x L mRNA was (15±1. 79)%, (28±2.34)%, (40±3.47)%, (20±1.54)% in 4 h, 6 h, 8 h, 15 h, respectively, but it was less than 15% in control group. It was concluded that NF-κB was involved in regulating bcl-x transcription. It was suggested that NF-κB was an important factor for drug resistance in leukemia cells.