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Published on: November 11, 2021
Mesenchymal Stem Cell-Conditioned Media-Derived Exosomes Loaded With Grifola frondosa Extract Inhibit Lung Cancer via
1Department of Thoracic Surgery The First Affiliated Hospital of Xi'an Jiaotong University Xi'an China.
Abstract:
The increasing prevalence of drug resistance diminishes the efficacy of chemotherapy and other therapeutic modalities for individuals diagnosed with lung cancer. Therefore, it is imperative to develop novel treatment approaches. This study examined how mesenchymal stem cell-derived exosomes containing extraction of Grifola frondosa (G. frondosa) affected lung cancer cells. Exosomes were obtained from mesenchymal stem cells and loaded with G. frondosa extract (extract-exosomes) by sonication. The effects of extract-exosomes on A549 lung cancer cells were assessed in vitro on cell viability, colony formation, mitochondrial membrane disruption, migration, apoptosis, autophagy, and cell cycle. Moreover, we examined apoptosis-related genes mRNA expression by real-time PCR. Finally, both NF-κB and MAPK signaling pathways were evaluated by western blotting method. Our results indicated that exposure to extract-exosomes significantly inhibits lung cancer cells proliferation, colony formation, and migration. Furthermore, this treatment increased mitochondrial membrane disruption, apoptosis, and autophagy in the cancer cells. Additionally, there was a notable increase in the number of the treated cancer cells at G1 and sub-G1 phases of the cell cycle. The research findings indicate that extract-exosomes can inhibit lung cancer cells proliferation through the induction of apoptosis and autophagy, cell cycle arrest, as well as modification of NF-κB and MAPK pathways.
Insights
Mesenchymal stem cell-derived exosomes loaded with Grifola frondosa extract inhibit lung cancer cell growth. This novel approach induces apoptosis and autophagy, offering a potential new treatment for lung cancer.
Area of Science:
- Biomedical Science
- Cancer Research
- Drug Discovery
Background:
- Drug resistance limits chemotherapy efficacy in lung cancer patients.
- Novel therapeutic strategies are urgently needed to combat lung cancer.
- Mesenchymal stem cell-derived exosomes offer a promising drug delivery platform.
Purpose of the Study:
- To investigate the anti-cancer effects of Grifola frondosa extract-loaded exosomes on lung cancer cells.
- To evaluate the impact of these exosomes on cancer cell viability, proliferation, migration, and apoptosis.
- To explore the underlying molecular mechanisms, including cell cycle regulation and signaling pathways.
Main Methods:
- Exosomes were isolated from mesenchymal stem cells and loaded with Grifola frondosa extract via sonication.
- In vitro assays were performed on A549 lung cancer cells to assess cell viability, colony formation, mitochondrial membrane potential, migration, apoptosis, and autophagy.
- Apoptosis-related gene expression was analyzed using real-time PCR, and NF-κB and MAPK signaling pathways were evaluated by western blotting.
Main Results:
- Extract-exosomes significantly inhibited lung cancer cell proliferation, colony formation, and migration.
- Treatment with extract-exosomes increased mitochondrial membrane disruption, apoptosis, and autophagy in cancer cells.
- Cell cycle analysis revealed an accumulation of treated cells in the G1 and sub-G1 phases.
Conclusions:
- Grifola frondosa extract-loaded exosomes demonstrate potent anti-cancer activity against lung cancer cells.
- The mechanism involves the induction of apoptosis and autophagy, cell cycle arrest, and modulation of NF-κB and MAPK signaling pathways.
- This exosome-based therapeutic approach holds potential for developing novel lung cancer treatments.
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