| Lung cancer is the most common cause of cancer-related deaths worldwide.However,the overall cure and survival rates for lung cancer still remain low.Hence continued research into new therapeutic strategies is urgently required to improve outcomes for lung cancer.Mesenchymal stem cells(MSCs)are multipotent progenitor cells which can be isolated from various tissues.Owe to their immune privilege,immune regulatory and injured/tumor site migrating properties,MSCs have become one of the most commonly employed cell types for clinical therapeutic applications including cancer treatment.However,the effect of MSCs on lung cancer cells is controversial,and the underlying mechanisms remain unclear,which harms the utilization of MSCs in tumor therapy.In this study,we use CCK-8 Assay,LDH assay,Flow cytometry analysis,Wound healing assay,transwell assay,qPCR and western blot exploredthe effect and mechanisms of MSCs on A549 cells.We found that human umbilical cord MSC-conditioned media(MSC-CM)promote EMT,invasion and migration nonetheless inhibit proliferation and promote apoptosis of lung cancer cells.The EMT promoting effect of MSCs could be mediated by exosomes derived from MSCs(MSC-exo)and eliminated through inhibiting the release of the exosomes.Moreover,silencing TGF-β1 expression in MSCs can revert the EMT promoting effect and enhance the anti-proliferative and pro-apoptotic effect of MSCs on lung cancer cells via MSC-exo.Further investigation found that Smad2/3,AKT/GSK-3β/β-catenin,NF-κB,ERK,JNK and p38 MAPK in TGF-β1signaling pathways could be activated by MSC-exo in lung cancer cells,while silencing TGF-β1 expression in MSCs may deactivate these pathways.These findings might suggest a safe therapeutic possibility for employing MSCs in lung cancer therapy. |
