PURPOSE: Bcl-2, an inhibitor of apoptosis frequently shows elevated expression 
in human tumors, thus resulting in resistance to radiation therapy. Therefore, 
inhibiting Bcl-2 function may enhance the radiosensitivity of tumor cells. 
Tetrocarcin A (TC-A) and bcl-2 antisense oligonucleotides exhibit antitumor 
activity by inhibiting Bcl-2 function and transcription, respectively. We 
investigated whether these antitumor agents would enhance the cytotoxic effects 
of radiation in tumor cells overexpressing Bcl-2.
METHODS AND MATERIALS: We used HeLa/bcl-2 cells, a stable Bcl-2-expressing cell 
line derived from wild-type HeLa (HeLa/wt) cells. Cells were incubated with TC-A 
and bcl-2 antisense oligonucleotides for 24 h after irradiation, and cell 
viability was then determined. Apoptotic cells were quantified by flow 
cytometric assay.
RESULTS: The HeLa/bcl-2 cells were more resistant to radiation than HeLa/wt 
cells. At concentrations that are not inherently cytotoxic, both TC-A and bcl-2 
antisense oligonucleotides increased the cytotoxic effects of radiation in 
HeLa/bcl-2 cells, but not in HeLa/wt cells. However, in HeLa/bcl-2 cells, 
additional treatment with TC-A in combination with radiation did not 
significantly increase apoptosis.
CONCLUSIONS: The present results suggest that TC-A and bcl-2 antisense 
oligonucleotides reduce radioresistance of tumor cells overexpressing Bcl-2. 
Therefore, a combination of radiotherapy and Bcl-2 inhibitors may prove to be a 
useful therapeutic approach for treating tumors that overexpress Bcl-2.