ABT-737 reverses the acquired radioresistance of breast cancer cells by targeting Bcl-2 and Bcl-xL

Background: acquired radioresistance of cancer cells remains a fundamental barrier to attaining the maximal efficacy of radiotherapy for the treatment of breast cancer. anti-apoptotic proteins,such as bcl-2 and bcl-xl,play an important role in the radioresistance of cancer cells. in the present study,we aimed to determine if abt-737,a bh3-only mimic,could reverse the acquired radioresistance of the breast cancer cell line mda-mb-231r by targeting bcl-2 and bcl-xl. methods. the radiosensitivity of mda-mb-231 and mda-mb-231r cells was compared using colony formation assays. reverse-transcription pcr and western blot were performed to detect the expression of bcl-2 and bcl-xl in the cancer cell lines. annexin v flow cytometric analysis and caspase-3 colorimetric assay were used to evaluate apoptosis of the cancer cells. cell viability was measured using the cell counting kit-8. the animals used in this study were 4 to 6-week-old athymic female balb/c nu/nu mice. results: the mda-mb-231r cells were more radioresistant than the mda-mb-231 cells,and bcl-2 and bcl-xl were overexpressed in the mda-mb-231r cells. while abt-737 was able to restore the radiosensitivity of the mda-mb-231r cells in vitro and in vivo experiment,it was not able to enhance the radiosensitivity of the mda-mb-231 cells. in addition,abt-737 increased radiation-induced apoptosis in the mda-mb-231r cells. bcl-2 and bcl-xl were down regulated in the mda-mb-231r cells following treatment with abt-737. conclusions: targeting of the anti-apoptotic proteins bcl-2 and bcl-xl with abt-737 may reverse the acquired radioresistance of mda-mb-231r cells in vitro and in vivo. these findings suggest an attractive strategy for overcoming the acquired radioresistance of breast cancer cells. © 2012 li et al.; licensee biomed central ltd.