Multidimensional screening of Astragalus membranaceus small molecules to mitigate carbon ion radiation-induced bystander effects

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.