Effects of transforming growth factor beta-1 infected human bone marrow mesenchymal stem cells on high- and low-metastatic potential hepatocellular carcinoma

Background: This study investigates the effects of human bone marrow-derived mesenchymal stem cell (hMSC) on migration and proliferation ability of hepatocellular carcinoma (HCC) with high- and low-metastatic potential. Methods: The hMSC and transforming growth factor-beta 1 (TGF beta-1) gene infected hMSC were co-cultured with hepatoma cells. The ability of cells migration was assessed by Transwell assay. The ability of cells proliferation was detected using CCK-8 assay. The mice were engrafted with hMSC and TGF beta-1 gene infected hMSC, respectively, after hepatoma cells inoculation 15 days, twice a week for 6 weeks successively. The tumor inhibition rate was calculated. TGF beta-1, osteopontin (OPN), and programmed cell death protein 4 (PDCD4) genes expression of hepatoma cells were detected by quantitative real-time polymerase chain reaction (qPCR) before and after co-cultured experiments. Results: TGF beta-1 infected hMSC or hMSC co-culture with hepatoma cells groups can significantly promote hepatoma cells proliferation (P < 0.05). The migration numbers of hepatoma cells with TGF beta-1 infected hMSC co-culture groups were significantly reduced compared with the other two groups (P < 0.05). The tumors weight inhibition rates of MHCC97-H and MHCC97-L animal models were the highest in the third week by hMSC engraftment. But the highest tumor inhibition rate of MHCC97-H animal models was observed in the fourth week and MHCC97-L animal models in the fifth week after TGF beta-1 infected hMSC engraftment. OPN gene relative quantitative expression of hepatoma cells was significantly down-regulated after co-cultured with hMSC and TGF beta-1 gene infected hMSC groups (P < 0.05). TGF beta-1 gene relative quantitative expression of MHCC97-H and MHCC97-L cells was significantly up-regulated after co-cultured with TGF beta-1 gene infected hMSC groups (P < 0.05). PDCD4 expression had no statistical differences among groups. Conclusions: hMSC and TGF beta-1 gene infected hMSC can promote hepatoma cells proliferation and inhibit hepatoma cells migration. hMSC and TGF beta-1 gene infected hMSC exhibit anti-tumor activity in a time-dependent manner. TGF beta-1 cytokine may be the main factor in HCC proliferation. OPN makes a significant contribution to the changes of hepatoma cells metastasis.National Science Foundation of China [81271607]; Natural Science Foundation of Fujian Province, China [2013 J01392]SCI(E)PubMedARTICLEcjr.luguangming@vip.163.com562