Background:This study explores the therapeutic potential of radiodynamic therapy (RDT), a combination of the photosensitizer 5-aminolevulinic acid (5-ALA) administration and X-ray irradiation, for high-grade glioma (HGG). The research aims to verify the RDT efficacy in both normoxic and hypoxic environments, examine its mechanisms, and assess its impact on the tumor micro-immune environment to address resistance to RDT.Methods:Glioma cell lines U87MG and U251MG were used in experiments in vitro. The cells were divided into four groups with or without 5-ALA and X-ray exposure.Results:Results demonstrated that RDT was effective under normoxia (20% O2), increasing reactive oxygen species (ROS) production and significantly decreasing U87MG cell viability in a 5-ALA concentration-dependent manner at 2 Gy and 6 Gy. However, under hypoxic conditions (3% O2) or long-term 3% O2exposure, the RDT effect was not significant compared to controls. The study also found that RDT under normoxia influenced immune reaction-related gene expression, while under hypoxia, it primarily affects genes related to epithelial–mesenchymal transition (EMT). Further analysis revealed that RDT reduces the secretion of soluble PD-L1, a marker of immune checkpoint inhibition, in a 20% O2environment. Additionally, RDT suppressed the vascular endothelial growth factor (VEGF), an angiogenesis marker, under 3% O2conditions. RDT also reduced the secretion of colony-stimulating factor -1 (CSF-1), a differentiation inhibitory marker for macrophages, in a 20% O2environment.Conclusion:In conclusion, this study provides evidence that RDT, combining 5-ALA and X-ray irradiation, has potential as a therapeutic strategy for HGG, especially under normoxic conditions. It may also offer benefits under hypoxia, particularly in inhibiting angiogenesis. The study also highlights the importance of understanding the role of oxygen levels in the efficacy of RDT and its potential impact on immune responses, angiogenesis, and macrophage differentiation in the tumor microenvironment. Further research is needed to fully elucidate the underlying mechanisms and optimize RDT for clinical application.
背景：本研究探讨了放射动力疗法（RDT）——即光敏剂5-氨基酮戊酸（5-ALA）给药联合X射线照射——治疗高级别胶质瘤（HGG）的潜在疗效。研究旨在验证RDT在常氧与缺氧环境下的有效性，探究其作用机制，并评估其对肿瘤微免疫环境的影响，以应对RDT耐药性问题。 方法：实验采用胶质瘤细胞系U87MG和U251MG进行体外研究。细胞被分为四组，分别接受含或不含5-ALA及X射线照射的处理。 结果：研究结果显示，在常氧条件（20% O₂）下，RDT能有效增加活性氧（ROS）生成，并在2 Gy和6 Gy照射剂量下以5-ALA浓度依赖的方式显著降低U87MG细胞活力。然而在缺氧条件（3% O₂）或长期3% O₂暴露下，RDT效果与对照组相比无显著差异。研究还发现，常氧条件下的RDT会影响免疫反应相关基因表达，而缺氧条件下则主要影响上皮-间质转化（EMT）相关基因。进一步分析表明，在20% O₂环境中，RDT能降低可溶性程序性死亡配体1（sPD-L1）的分泌——这是免疫检查点抑制的标志物。此外，在3% O₂条件下，RDT可抑制血管内皮生长因子（VEGF）这一血管生成标志物。在20% O₂环境中，RDT还能减少巨噬细胞分化抑制标志物集落刺激因子-1（CSF-1）的分泌。 结论：本研究证实，5-ALA联合X射线照射的RDT具有作为HGG治疗策略的潜力，尤其在常氧条件下效果显著。在缺氧环境中也可能产生治疗获益，特别是在抑制血管生成方面。研究同时强调了理解氧浓度水平对RDT疗效影响的重要性，及其对肿瘤微环境中免疫应答、血管生成和巨噬细胞分化的潜在调控作用。未来需要进一步研究以全面阐明其作用机制，并优化RDT的临床应用方案。
肿瘤(癌症)患者之家