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Ginsenoside Rg3 promotes chemosensitivity in lung adenocarcinoma organoids via apoptotic pathways
Min Liu1,2, Yanxia Li2,3, Bing Han2,3,4
1Department of Pathology, Tianjin Fifth Central Hospital, Tianjin, China.
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.
Insights
Ginsenoside Rg3 enhances cisplatin
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Platinum-based chemotherapy is standard for advanced non-small cell lung cancer (NSCLC).
- Chemoresistance limits treatment efficacy in NSCLC.
- Ginsenoside Rg3 shows potential as a chemosensitizer.
Purpose of the Study:
- To evaluate the chemosensitizing effect of Ginsenoside Rg3 on cisplatin in lung adenocarcinoma.
- To investigate the mechanisms of Ginsenoside Rg3 in overcoming chemoresistance.
- To validate patient-derived organoids (PDOs) as a model for personalized drug response.
Main Methods:
- Established and characterized three lung adenocarcinoma patient-derived organoid (PDO) lines.
- Assessed the effect of Ginsenoside Rg3 and cisplatin combination on organoid viability and IC50.
- Measured intracellular reactive oxygen species (ROS) levels and apoptosis via TUNEL assay.
Main Results:
- The combination of Ginsenoside Rg3 and cisplatin significantly inhibited organoid viability more than either agent alone.
- Combination therapy reduced the half-maximal inhibitory concentration (IC50) of cisplatin.
- Treatment increased intracellular ROS levels and induced apoptosis.
Conclusions:
- Ginsenoside Rg3 acts as a potent chemosensitizer for cisplatin in lung adenocarcinoma.
- PDOs are a valuable platform for predicting personalized drug responses.
- Ginsenoside Rg3 warrants further investigation as an adjunct therapy for chemoresistant NSCLC.
