Ginsenoside Rg3 promotes chemosensitivity in lung adenocarcinoma organoids via apoptotic pathways

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.

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.

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.

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.