Ginsenoside Rg3 promotes chemosensitivity in lung adenocarcinoma organoids via apoptotic pathways.

INTRODUCTION: Platinum-based chemotherapy remains a cornerstone for advanced non-small cell lung cancer (NSCLC), but its efficacy is often compromised by chemoresistance, necessitating strategies to restore drug sensitivity. Ginsenoside Rg3, an active component of Panax ginseng, exhibits anti-tumor and potential chemosensitizing properties, though its mechanisms in clinically relevant models are not fully understood. METHODS: We successfully established and characterized three lung adenocarcinoma patient-derived organoid (PDO) lines that faithfully recapitulated the histopathological and molecular features of the parental tumors. The chemosensitizing effect of Rg3 on cisplatin was evaluated by assessing organoid viability, half-maximal inhibitory concentration (IC50), intracellular reactive oxygen species (ROS) levels, and apoptosis via TUNEL assay. RESULTS: Pharmacodynamic evaluation revealed that the combination of Rg3 and cisplatin exerted superior inhibitory effects on organoid viability compared to either agent alone, with a pronounced reduction in IC50. Furthermore, the combination treatment significantly increased intracellular ROS levels and induced apoptosis, as evidenced by TUNEL assay. DISCUSSION: This study provides preclinical evidence for Rg3 as a promising chemosensitizer in lung adenocarcinoma and highlights the value of PDOs as a robust platform for personalized drug response profiling. These findings support further exploration of Rg3 as an adjunct to platinum-based chemotherapy in overcoming chemoresistance.