Mesenchymal Stem Cell‐Conditioned Media‐Derived Exosomes Loaded With Grifola frondosa Extract Inhibit Lung Cancer via NF‐κB and MAPK Pathway Modulation

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.