加入脐带间充质干细胞来源外泌体培养的肝癌细胞生物学行为变化及其机制OACSTPCD

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.