辐射研究与辐射工艺学报2025,Vol.43Issue(6):38-46,9.DOI:10.11889/j.1000-3436.2025-0060
Tspan4介导的迁移体在肺癌细胞重离子辐射效应中的作用
Role of Tspan4-mediated migrasomes in the heavy ion radiation effects on lung cancer cells
摘要
Abstract
Migrasomes play a crucial role in regulating the tumor microenvironment(TME),mediating tumor metastasis,and influencing the prognosis of tumor therapy.In this study,lung cancer A549 cells were used as a model to explore the mechanism of Tspan4-mediated migrasomes in the effects of heavy ion radiation.The experiment employed 12C6+ion beams(80 MeV/u,LET 30 keV/μm)for irradiation treatment to analyze the effect on migrasome formation.Furthermore,methods including migrasome quantitative analysis,wound healing assay,Transwell migration assay,Western blotting,colony formation assay,γH2AX foci detection,and apoptosis analysis were used to systematically evaluate the radiation effects.The experimental results showed that 12C 6+ion beams significantly inhibited the migration ability of A549 cells(with a 33%reduction in wound healing distance)and the formation of migrasomes(p<0.001).Moreover,Tspan4 knockout further synergistically enhanced these effects:the expression levels of migration-related proteins ITGA5 and MMP9 were downregulated,the colony formation ability was significantly reduced,the formation rate of γH2AX foci increased by 2.3 times,and the apoptosis rate rose to 4.74 times that of the control group(p<0.001).This study indicates that Tspan4 knockout enhances the interference of 12C 6+ion beams with DNA damage repair and the induction of apoptosis by disrupting migrasome-dependent intercellular communication and inhibiting tumor microenvironment remodeling.It provides a new theoretical basis for the targeted strategy of"migrasome combined with heavy ion radiotherapy.关键词
迁移体/肺癌/重离子/辐射效应Key words
Migrasome/Lung cancer/Heavy ion/Radiation effect分类
医药卫生引用本文复制引用
马丽娟,黄雅丽,吴庆丰,杜亚蓉,王菊芳..Tspan4介导的迁移体在肺癌细胞重离子辐射效应中的作用[J].辐射研究与辐射工艺学报,2025,43(6):38-46,9.基金项目
兰州市城关区科技计划项目(2024-11-4)和国家自然科学基金项目(12175289) Supported by Science and Technology Research Project of Chengguan District,Lanzhou City(2024-11-4)and National Natural Science Foundation of China(12175289) (2024-11-4)