Vanillic acid inhibits TGF-β type I receptor to protect bone marrow mesenchymal stem cells from radiation-induced bystander effects

作者：Ting Zhou, Yiming Zhang, Gu-Cheng Zhou, Fu-Xian Liu, Zhiming Miao, Liying Zhang, Yangyang Li, Zhiwei Liu, Shang-Zu Zhang, Jing Li, Fan Niu, Yan Chen, Yongqi Liu · 发表于：Translational Cancer Research · 年份：2025 · DOI：10.21037/tcr-24-1080 · 被引用次数：2 · 研究领域：Inflammatory mediators and NSAID effects

Background: Radiotherapy is a major treatment option for non-small cell lung cancer (NSCLC); however, irradiated tumor cells can damage non-irradiated cells through radiation-induced bystander effects (RIBE), which can affect the therapeutic efficacy. The study aimed to investigate the mechanism underlying RIBE and the protective effects of vanillic acid (VA) on human bone marrow mesenchymal stem cells (BMSCs). Methods: We established two irradiation models to investigate RIBE. First, we established the A549 cell irradiation model alone, and tested the expression of cathepsin B (CTSB) and transforming growth factor-beta 1 (TGF-β1) by western blot and immunofluorescence staining. Next, we established a co-culture model of A549 cells and BMSCs. After 2 Gy X-rays irradiation of A549 cells, BMSCs cell viability was detected using Cell Counting Kit-8 (CCK-8), reactive oxygen species (ROS) level was detected using flow cytometry, and CTSB, TGF-β type I receptor (TGFβRI), p62 (sequestosome 1), BECLIN1, microtubule-associated protein light chain 3 (LC3), etc., were detected using western blot. Phosphorylated histone H2AX (γH2AX), CTSB, lysosomal-associated membrane protein 1 (LAMP1), and TGFβRI expression levels were detected by immunofluorescence staining. Molecular docking and molecular dynamics simulation, and a CCK-8 assay were used to screen for molecules from Astragalus membranceus that inhibited TGFβRI activity, to protect BMSCs from RIBE. Lastly, we validated VA activity in v...