Autophagy inhibition can overcome radioresistance in breast cancer cells through suppression of TAK1 activation.

BACKGROUND/AIM: Autophagy is frequently activated in radioresistant cancer cells. In the present study, we evaluated the role of autophagy and transforming growth factor-activated kinase 1 (TAK1) in radioresistance.

MATERIALS AND METHODS

TAK1 phosphorylation in MDA-MB231 breast cancer cells was evaluated by western blotting. The regulatory effects of the TAK1 inhibitor and autophagy inhibitor were assessed by cell morphology, cell survival and induction of apoptosis.

RESULTS

Radiation induced the phosphorylation of TAK1, whereas the inhibition of TAK1 activity enhanced the cytotoxicity of radiation in MDA-MB231 cells. Autophagy inhibitors significantly enhanced radiation-induced apoptosis of MDA-MB231 cells. This augmentation in radiosensitivity seemed to result from the suppression of TAK1 activation.

CONCLUSION

Inhibition of autophagy enhanced radiosensitivity through suppression of radiation-induced TAK1 activation, suggesting that the modulation of TAK1-induced autophagy may be a good therapeutic strategy to treat radioresistant breast cancer.