Raddeanin A Improves the Therapeutic Effect of Osimertinib in NSCLC byAccelerating ROS/NLRP3-mediated Pyroptosis

作者：Liping Lin, Xuan Wu, Yuanxue Jiang, Xi Luo, Xiaolong Cao · 发表于：Current Pharmaceutical Design · 年份：2023 · DOI：10.2174/0113816128263069231010111347 · 被引用次数：4 · 研究领域：Inflammasome and immune disorders、Lung Cancer Treatments and Mutations、Genomics, phytochemicals, and oxidative stress

BACKGROUND: Osimertinib (Osm) is the preferred treatment for non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) T790M mutation. Nevertheless, the resistance of NSCLC cells to Osm will eventually develop, which remains the biggest obstacle to treating such diseases. Raddeanin A (RA) exhibits a potent anti-tumor effect on various types of cancer cells. In this study, we aimed to investigate whether RA suppresses NSCLC growth and increases the therapeutic effect of Osm. METHODS: The effects of RA on inhibiting NSCLC cell viability and proliferation were tested using cell counting kit 8 (CCK-8) and EdU assay. The roles of RA in improving the anti-tumor effect of Osm were tested with CCK-8 and colony formation assays. The roles of RA in regulating reactive oxygen species (ROS)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)-mediated pyroptosis were assessed using quantitative real- time PCR (qRT-PCR) and western blotting analysis. RESULTS: . Mechanistically, RA induced ROS overgeneration and resulted in subsequent NLRP3-mediated pyroptosis. In particular, combination treatment with Osm and RA reduced cell viability and clonogenic growth capacity more efficiently than Osm mono treatment in A549 and H1975 cells. Combination treatment also promoted NLRP3-mediated pyroptosis more efficiently than Osm mono treatment. CONCLUSION: RA inhibited the NSCLC growth and increased the anti-tumor role of Osm in NSCLC by facilitating ROS/NLRP3-m...