The role of mitophagy in radioresistance of cancers

以人癌细胞(HCT8、A549、MCF7和MDA-MB-453)为研究对象。5GyX射线照射后8、24、48h，癌细胞γ损伤标志物(DNAH_2AX)、细胞周期蛋白依赖性激酶抑制物(P21)的表达显著增加，线粒体超氧化物歧化水平显著升高。这表明辐射暴露可诱导有丝分裂活性。为了验证有丝分裂在调节癌细胞辐射抗性中的作用，我们使用小干扰RNA来敲除辐射诱导的有丝分裂受体的表达。Western印迹分析显示，5GyX射线照射后48h，部分辐射诱导的吞线体受体被敲除后，癌细胞中γ、H_2AX的表达和线粒体超氧化物歧化水平均升高。我们仍在研究关键的有丝分裂受体的过度表达如何影响癌细胞的辐射抗性。我们的数据表明，有丝分裂可能调节放射治疗后癌症的获得性辐射抗性。

Human cancer cells (HCT8, A549, MCF7 and MDA-MB-453) were used in this study. The expression of DNA damage marker (γH2AX), cyclin-dependent kinase inhibitor (p21), and the level of mitochondrial superoxide were significantly increased in human cancer cells 8, 24, and 48 hours after 5 Gy X-rays exposure.Interestingly, radiation exposure significantly increased the expression of several mitophagy receptors 48 hours after 5 Gy X-rays exposure, but not 8 or 24 hours after 5 Gy X-rays exposure. It suggests that radiation exposure induces mitophagy activity. To verify the role of mitophagy in regulating the radioresistance of cancer cells, we used small interfering RNA to knockdown the expression of radiation-induced mitophagy receptors. Western blot analysis showed that the knockdown of some radiation-induced mitophagy receptors enhanced the expression of γH2AX and the level of mitochondrial superoxide in cancer cells 48 hours after 5 Gy X-rays exposure. We are still investigating how the overexpression of the key mitophagy receptors will affect the radioresistance of cancer cells.Our data suggests that mitophagy may regulate the acquired radioresistance of cancers following radiotherapy.