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OBJECTIVE To determine whether Bcl-2 protein down-regulation can render NCI-460 cells more susceptible to gamma radiation-induced apoptosis by treatment with antisense oligonucleotide (ASODN) against the coding region of Bcl-2 mRNA.METHODS Cell survival was determined using the trypan blue dye exclusion. Expression of the Bcl-2 protein was assayed using immunofluorescence labeling with fluoresce isothiocyanate. Apoptosis was determined by Giemsa staining and flow cytomertry.RESULTS It was found that Bcl-2 ASODN combined with radiation significantly reduced the number of viable cells (P＜0.05). There was no difference in cell survival between a nonsense oligodeoxynucleotide/radiation combination and cells treated with radiation alone. Bcl-2 ASODN combined with radiation significantly inhibited expression of the Bcl-2protein in the NCI-H460 cells (P＜0.05). Using Giemsa staining, cells treated with Bcl-2 ASODN combined with radiation at 72 h displayed classic apoptotic changes. Apoptotic rates of the NCI-H460 cells treated with Bcl-2 ASODN combined with radiation significantly increased (P＜0.05), compared with either a nonsense oligodeoxynucleotide/radiation combination or radiation-treatment cells alone.CONCLUSION ASODN against the coding region of Bcl-2 mRNA increases radiation-induced apoptosis in NCI-H460 cells.