Inhibitory effect and mechanism of mesenchymal stem cells on liver cancer cells

Mesenchymal stem cells (MSCs), with their capacity for self-renewal and differentiation into various cell types, are important seed cells for stem cell therapy. MSCs exhibit potent pathotropic migratory properties that make them attractive for use in tumor prevention and therapy. However, little is known about the underlying molecular mechanisms that link MSCs to the targeted tumor cells. This study investigated the inhibitory effect and mechanism of MSCs on human hepatoma HepG₂ cells using co-culture and conditioned medium system and animal transplantation model. The HepG₂ cells were co-cultured with MSCs or treated with conditional media derived from MSCs cultures in vitro. Results of methylthiazolyldiphenyl tetrazolium assay and flow cytometric assay showed that the proliferation and apoptosis of HepG₂ cells decreased and increased, respectively. Reverse transcription polymerase chain reaction analysis showed that the expression levels of bcl-2, c-Myc, β-catenin, and survivin were downregulated. The results of enzyme-linked immunosorbent assay and Western blot proved that MSCs secreted Dkk-1 to inhibit the expression of Wnt signaling pathway-related factors (bcl-2, c-Myc, β-catenin, and survivin) in tumor cells, consequently inhibiting the proliferation and promoting the apoptosis of HepG₂ cells. Animal transplantation experiment showed that tumor growth was significantly inhibited when HepG₂ cells were co-injected with MSCs into nude mice. These results suggested that MSCs inhibited the growth and promoted the apoptosis of HepG₂ cells in a dose-dependent manner. This study provided a new approach and experimental basis for cancer therapy. This study also proved that the Wnt signaling pathway may have a function in MSC-mediated tumor cell inhibition.