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image of Exosome-mediated Induction of Apoptosis in Cisplatin-treated Gastric Cancer Cells as a Strategy to Mitigate Side Effects

Abstract

Background

Gastric cancer is the third most lethal malignancy worldwide. While cisplatin has shown remarkable efficacy at a low cost, it is also associated with severe side effects. Exosomes play a key role in mediating the bystander effect of radiation and have the capacity to deliver apoptosis signals for targeted destruction of tumor cell. However, there remains a paucity of research on exosome-mediated bystander effects in the context of chemotherapeutic drugs.

Objective

This study aims to investigate the ability of cisplatin-induced exosomes to deliver apoptosis signals to gastric cancer cells, with the aim of mitigating the adverse effects associated with chemotherapy.

Methods

Differential ultracentrifugation was used to isolate apoptotic exosomes secreted by cisplatin-induced gastric cancer MKN-28 cells. Characterization and identification of these exosomes were performed by transmission electron microscopy, particle size analyzer, flow cytometry, and Western blotting. The transduction efficiency of the exosomes was confirmed through immunefluorescence. The effects of apoptotic exosomes on the proliferation, apoptosis, migration, cycle, senescence, and tumor formation of MKN-28 cells and were investigated by live cell workstation, flow cytometry, HE staining, and tumorigenicity assays.

Results

Cisplatin-induced apoptotic exosomes, termed DDP-EXO, exhibited a significantly enhanced inhibitory effect on the proliferation of MKN-28 cells compared to gastric epithelial GES-1 cells. Moreover, DDP-EXO was able to deliver apoptotic signals to MKN-28 cells, leading to an increase in the apoptotic population in recipient cells, possibly through the involvement of Caspase-9. Furthermore, DDP-EXO showed limited impacts on cell migration, cell cycle, or cell senescence. , DDP-EXO effectively suppressed tumorigenesis in a subcutaneous tumor model without causing detectable pathological changes in main organs and blood samples, suggesting a favorable safety profile.

Conclusion

In summary, this study provides new perspectives on the potential application of exosomes as an innovative therapeutic approach for gastric cancer.

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2025-05-12
2025-09-14

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/content/journals/ccdt/10.2174/0115680096369817250407164352
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Exosome-mediated Induction of Apoptosis in Cisplatin-treated Gastric Cancer Cells as a Strategy to Mitigate Side Effects
Bentham Science Publishers ; https://doi.org/10.2174/0115680096369817250407164352
/content/journals/ccdt/10.2174/0115680096369817250407164352
/content/journals/ccdt/10.2174/0115680096369817250407164352
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  • Article Type:     Research Article
Keywords: Gastric cancer ; cisplatin ; bystander effects ; exosomes

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