Antisense bcl-2 therapy combined with chemotherapy has been proved to be effective in various tumors. However, the role played by antisense bcl-2 therapy alone is not clear. In this study, we compared the apoptosis and the protein profiles of antisense bcl-2 transfected human neuroblastoma SK-N-MC cells to the control cells. Flow cytometric data indicated that antisense bcl-2 transfection did not lead to more extensive apoptosis in SK-N-MC cells (14.9 +/- 3.8%) than the control cells (10.3 +/- 2.3%). The above observation was confirmed by fluorescence microscopy using Hoechst 33258 staining. However, antisense bcl-2 induced changes in the expression of various proteins as shown by proteomic comparison, which included the up-regulation of the anti-apoptotic and anti-oxidant protein thioredoxin. By western blot validation, thioredoxin was found to be up-regulated by 2.9-folds with the corresponding down-regulation of Bcl-2 by 2.1-folds. The up-regulation of thioredoxin may be a compensating mechanism for cell survival in neuroblastoma when Bcl-2 expression is suppressed, and it may to some extent attenuate the effectiveness of antisense bcl-2 therapy.