多维筛选黄芪小分子以减轻碳离子辐射引起的旁观者效应。
Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects.
发表日期:2024 Oct
作者:
Liying Zhang, Yiming Zhang, Yangyang Li, Qiyang Li, Shangzu Zhang, Zhiming Miao, Jinpeng He, Ting Zhou, Gengqiang Yang, Xin Wang, Jufang Wang, Yongqi Liu
来源:
Journal of Pharmaceutical Analysis
摘要:
现有研究表明,黄芪(AM)及其活性成分黄芪多糖、洋葱、黄芪甲苷等可以减轻X射线辐射损伤。然而,目前还没有关于异甘草素(ISL)如何减弱碳离子放射治疗肺癌诱导的骨髓间充质干细胞(BMSC)的旁观者效应的研究。本研究旨在研究AM衍生的小分子ISL通过减弱BMSCs中碳离子辐射诱导的旁观者效应(RIBE)来增强放疗敏感性,以阐明其作用机制。在本研究中,我们建立了C57BL/6小鼠肺癌移植瘤体内模型和A549细胞与BMSCs体外共培养模型,并成功用碳离子处理模型。在进一步的工作中,我们使用流式细胞术、免疫荧光、Western blot、酶联免疫吸附测定(ELISA)、抑制剂、短发夹RNA(shRNA)、细胞计数试剂盒8(CCK-8)等方法来阐明其机制。在接下来的实验中,我们发现ISL联合碳离子放疗具有显着的抗肿瘤作用,并保护BMSC免受辐射损伤。本研究的目的是探讨 ISL 在体外和体内环境中增强肺癌细胞对放疗的敏感性和减弱 RIBE 的潜力。中药联合放射治疗是治疗非小细胞肺癌的一种有前景的创新疗法。这些结果为 ISL 作为潜在放射增敏剂选项的进一步临床开发奠定了理论基础。© 2024 作者。
Existing studies have shown that Astragalus membranaceus (AM) and its active ingredients astragalus polysaccharides, oninon, and astragalus methyl glycosides can attenuate X-ray radiation-induced injury. However, there are no studies on how isoliquiritigenin (ISL) attenuate the bystander effect of bone marrow mesenchymal stem cells (BMSCs) induced by carbon ion radiation therapy for lung cancer. This study aimed to investigate the AM-derived small molecule ISL to enhance radiotherapy sensitivity by attenuating the carbon ion radiation-induced bystander effect (RIBE) in BMSCs to elucidate its mechanism of action. In this study, we established a C57BL/6 mouse lung cancer transplantation tumor model in vivo and a co-culture model of A549 cells and BMSCs in vitro, and the models were successfully treated with carbon ions. In further work, we used flow cytometry, immunofluorescence, Western blot, enzyme-linked immunosorbent assay (ELISA), inhibitor, short hairpin RNA (shRNA), Cell Counting Kit-8 (CCK-8), and other methods to illustrate the mechanism. In the next experiments, we found that ISL combined with carbon ion radiotherapy had a significant anti-tumor effect and protected BMSCs from radiation damage. The aim of this study was to investigate the potential of ISL in enhancing the sensitivity of lung cancer cells to radiotherapy and attenuating RIBE in both in vitro and in vivo settings. Traditional Chinese medicine combined with radiation therapy is a promising and innovative treatment for non-small cell lung cancer. These results establish a theoretical foundation for further clinical development of ISL as a potential radiosensitizer option.© 2024 The Authors.