Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway

作者：Yiming Zhang, Zhiming Miao, Yaping Chen, Zhang-Bo Song, Yangyang Li, Zhiwei Liu, Gu-Cheng Zhou, Jing Li, Liangliang Shi, Yan Chen, Shang-Zu Zhang, Xiaohui Xu, Jinpeng He, Jufang Wang, Liying Zhang, Yongqi Liu · 发表于：Phytomedicine · 年份：2023 · DOI：10.1016/j.phymed.2023.155290 · 被引用次数：44 · 研究领域：Traditional Chinese Medicine Analysis、Effects of Radiation Exposure、Cancer, Hypoxia, and Metabolism

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence an...