Changes in biological behaviors of liver cancer cells cultured with umbilical cord mesenchymal stem cell-derived exosomes and the mechanism
Objective To investigate the effects of umbilical cord mesenchymal stem cell-derived exosomes(UC-MSCs-Exo)on the biological behaviors of hepatocellular carcinoma(HCC)cells and to explore the potential mechanisms.Methods MHCC-97H cells in the logarithmic growth phase were divided into two groups:UCMSCs-Exo group and con-trol group,which were added with 10 μg/mL UCMSCs-Exo and an equivalent volume of PBS,respectively.Clone forma-tion assay was used to assess colony formation rate,Scratch assay was used to measured the healing rates,and flow cytome-try was used to analyze the apoptosis.The mRNA and protein expression levels of epithelial-mesenchymal transition(EMT)-related markers(N-cadherin,Vimentin,and Snail)and apoptosis-related markers(Bcl-2 and Bax)were assessed by real-time fluorescent quantitative PCR and Western blotting.Transcriptome sequencing was used to screen the differen-tially expressed genes(DEGs),followed by Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Ge-nomes(KEGG)pathway analysis as well as Disease Ontology(DO)pathway enrichment analysis.Results The UC-MSCs-Exo group had a lower colony formation rate,and higher wound healing and apoptosis rates than the control group(all P<0.05).The mRNA and protein expression levels of N-cadherin,Vimentin,Snail,and Bax were significantly high-er,whereas Bcl-2 levels were lower in the UCMSCs-Exo group than in the control group(all P<0.05).Transcriptomic analysis identified 74 DEGs in the UCMSCs-Exo group,with 43 up-regulated genes and 31 down-regulated genes.GO en-richment analysis revealed that DEGs were predominantly enriched in extracellular region,CXCR chemokine receptor binding,cell proliferation,and metabolism.KEGG pathway analysis indicated DEGs mainly involved IL-17,TNF,TGF-β,and NF-κB signaling pathways.DO pathway analysis showed that DEGs primarily participated in colorectal cancer,liv-er cancer,and gastrointestinal and metabolic disorders.Conclusions UCMSCs-Exo inhibits HCC cell proliferation and promotes migration and apoptosis.These effects may be mediated by regulating IL-17,TNF,TGF-β,and NF-κB signaling pathways,thereby inducing EMT of HCC cells.
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