Effect of Bcl-2 on Apoptosis and Transcription Factor NF-kB Activation Induced by Adriamycin in Bladder Carcinoma BIU87 Cells

Abstract

Resistance to apoptosis is a major obstacle preventing effective therapy for malignancies. Bcl-2 plays asignificant role in inhibiting apoptosis. We reconstructed a stable human Bcl-2 transfected cell line, BIU87-Bcl-2, that was derived from the transfection of human bladder carcinoma cell line BIU87 with a plasmid vectorcontaining recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. A cell line transfected with the plasmid alone [pcDNA3.1(+)-neo] was also established as a control. BIU87 and BIU87-neo proved sensitive to adriamycin induced apoptosis,while BIU87-Bcl-2 was more resistant. In view of the growing evidence that NF-κB may play an important rolein regulating apoptosis, we determined whether Bcl-2 could modulate the activity of NF-κB in bladder carcinomacells. Stimulation of BIU87, BIU87-neo and BIU87-Bcl-2 with ADR resulted in an increase expression of NF-κB(p<0.001). The expression of NF-κB in BIU87-Bcl-2 was higher than in the other two cases, with a concomitantreduction in the IκBκ protein level. These results suggest that the overexpression of Bcl-2 renders human bladdercarcinoma cells resistant to adriamycin -induced cytotoxicity and there is a link between Bcl-2 and the NF-κBsignaling pathway in the suppression of apoptosis.