Nanoscale Exosomes Derived from Gingiva Mesenchymal Stem Cells for Radiotherapy-Induced Apoptosis in Non-Small Cell Lung Cancer Cells

The efficacy of radiotherapy (RT) for non-small celllung carcinoma(NSCLC) is often compromised by radioresistance. Consequently, thereis a pressing need for agents that can be administered in conjunctionwith RT. Recent research has highlighted the potential of mesenchymalstem cell (MSC)-secreted exosomes to either promote or inhibit tumorprogression and drug resistance. Gingival mesenchymal stem cells (GMSCs),which possess readily obtainable and highly proliferative properties,have previously demonstrated immunomodulatory and tissue engineeringcapabilities. The antitumor effect of nanoscale exosomes derived fromGMSCs has received limited attention in the literature, and theirpotential radiotherapy sensitizing effects have not been investigated.This study aimed to evaluate the efficacy of combining GMSCs-exo withRT in NSCLC both in vitro and in vivo. Our results revealed that theexosomes derived from GMSCs possess a cup-shaped morphology with anaverage diameter of approximately 142 nm. Moreover, the combined treatmentof GMSCs-exo and ionizing radiation (IR) exhibited enhanced efficacyin inhibiting proliferation and promoting apoptosis of NSCLC cells,as compared to IR treatment alone. These in vitro findings were furthercorroborated by the suppression of tumor growth in A549 subcutaneousxenograft models upon the administration of GMSCs-exo in combinationwith RT. Additionally, our investigation provides evidence that theprocess of apoptosis in NSCLC cells is linked to a decrease in PCNAexpression and an increase in Bax/Bcl-2. In sum, we found the emergingroles of GMSCs-exo in enhancing the efficacies of RT, thus providinginsights into the potential clinical applications of exosomes derivedfrom MSCs in tumor radiotherapy.

Automated summary

This study evaluated the efficacy of combining nanoscale exosomes derived from gingival mesenchymal stem cells (GMSCs) with radiotherapy (RT) in treating non-small cell lung carcinoma (NSCLC). The results showed that GMSCs-exo possessed a cup-shaped morphology with an average diameter of approximately 142 nm. The combination of GMSCs-exo and ionizing radiation (IR) demonstrated enhanced efficacy in inhibiting proliferation and promoting apoptosis of NSCLC cells, compared to IR treatment alone. In vivo experiments also confirmed the suppression of tumor growth upon administration of GMSCs-exo in combination with RT. Thus, this study highlights the potential clinical applications of MSC-derived exosomes in tumor radiotherapy.