The effect of bone marrow mesenchymal stem cells on highly metastatic MHCC97-H hepatocellular carcinoma cells following OPN and TGFβ1 gene silencing.

Abstract

The metastatic behavior of hepatocellular carcinoma (HCC) is one of the key factors that leads to poor prognosis. The aim of the current study was to determine the changes in metastasis and the proliferation potential of bone marrow mesenchymal stem cells (BMSCs) in high metastatic potential hepatocellular carcinoma (MHCC97-H) following gene silencing. The osteopontin (OPN) and transforming growth factor-β (TGFβ1) genes, which are associated with metastasis and tumor proliferation, were silenced in MHCC97-H cells. Transwell assays were used to evaluate the migration of MHCC97-H cells in vitro. Additionally, a murine model of MHCC97-H lung metastasis was established. Following OPN and TGFβ1 silencing, the migration of MHCC97-H cells was significantly reduced following BMSC intervention (P<0.01). Furthermore, there were few MHCC97-H cells in the lung tissues of the OPN- and TGFβ1-silenced animals, and their integrated optical density (IOD) value was significantly lower compared with controls (P<0.05). Immunofluorescence of lung metastasis in the MHCC97-H model revealed that there was no significant difference in the IOD value of integrin αvβ3 expression in the OPN- and TGFβ1-silenced groups compared with controls (P>0.05). The metastasis and proliferation potential of MHCC97-H following BMSC intervention were significantly reduced in vitro and in vivo, especially in the TGFβ1-silenced group. The decrease in the metastatic potential in gene-silenced MHCC97-H cells was not associated with integrin αvβ3 expression. Therefore, OPN and TGFβ1 may be potential targets for HCC treatment, and TGFβ1 may have a higher therapeutic potential for BMSC intervention.