The role of mitophagy in radioresistance of cancers

线粒体自噬在癌症放射抗性中的作用

• 批准号: 22K20795
• 负责人: YAN Chen
• 金额: $ 1.83万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-08-31 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22K20795/
• 关键词: Radioresistance; Mitophagy; Cancer

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.

本研究中使用人癌细胞（HCT 8、A549、MCF 7和MDA-MB-453）。5戈伊X射线照射后8、24和48小时，人癌细胞DNA损伤标志物（γ H 2 AX）、细胞周期蛋白依赖性激酶抑制因子（p21）的表达和线粒体超氧化物水平均显著增加，有趣的是，5戈伊X射线照射后48小时，辐射暴露显著增加了几种线粒体自噬受体的表达，但在5戈伊X射线照射后8小时或24小时则没有。这表明辐射暴露会诱导线粒体自噬活动。为了验证线粒体自噬在调节癌细胞的辐射抗性中的作用，我们使用小干扰RNA来敲低辐射诱导的线粒体自噬受体的表达。Western blot分析显示，5戈伊X射线照射48 h后，某些辐射诱导的线粒体自噬受体的敲除使γ H2 AX的表达和线粒体超氧化物水平增加。我们仍在研究关键线粒体自噬受体的过表达如何影响癌细胞的放射抵抗性。我们的数据表明线粒体自噬可能调节放疗后癌症的获得性放射抵抗。

项目成果

Extracellular matrix remodeling in irradiated lungs may favor cancer metastasis

受辐射肺部的细胞外基质重塑可能有利于癌症转移

• 发表时间: 2022
• 作者: Chen YAN;Tao-Sheng LI
• 通讯作者: Tao-Sheng LI