Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olymhic-Ro 43-Gil, Songpa-Gu, Seoul 138-736, Republic of Korea.
Anticancer Res. 2014 Mar;34(3):1449-55.
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.
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.
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.
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.
背景/目的：自噬在放射抵抗性癌细胞中经常被激活。在本研究中，我们评估了自噬和转化生长因子激活激酶 1（TAK1）在放射抵抗性中的作用。
通过 Western blot 检测 MDA-MB231 乳腺癌细胞中 TAK1 的磷酸化。通过细胞形态、细胞存活和诱导细胞凋亡来评估 TAK1 抑制剂和自噬抑制剂的调节作用。
辐射诱导 TAK1 的磷酸化，而 TAK1 活性的抑制增强了 MDA-MB231 细胞中辐射的细胞毒性。自噬抑制剂显著增强了 MDA-MB231 细胞中辐射诱导的细胞凋亡。这种放射敏感性的增强似乎是由于抑制了 TAK1 的激活。
通过抑制辐射诱导的 TAK1 激活，抑制自噬增强了放射敏感性，提示调节 TAK1 诱导的自噬可能是治疗放射抵抗性乳腺癌的一种良好治疗策略。
