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

Abstract：

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-β1 (TGFβ-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 TGFβ-1 gene infected hMSC, respectively, after hepatoma cells inoculation 15 days, twice a week for 6 weeks successively. The tumor inhibition rate was calculated. TGFβ-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:TGFβ-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 TGFβ-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 TGFβ-1 infected hMSC engraftment. OPN gene relative quantitative expression of hepatoma cells was significantly down-regulated after co-cultured with hMSC and TGFβ-1 gene infected hMSC groups (P < 0.05). TGFβ-1 gene relative quantitative expression of MHCC97-H and MHCC97-L cells was significantly up-regulated after co-cultured with TGFβ-1 gene infected hMSC groups (P < 0.05). PDCD4 expression had no statistical differences among groups. CONCLUSIONS:hMSC and TGFβ-1 gene infected hMSC can promote hepatoma cells proliferation and inhibit hepatoma cells migration. hMSC and TGFβ-1 gene infected hMSC exhibit anti-tumor activity in a time-dependent manner. TGFβ-1 cytokine may be the main factor in HCC proliferation. OPN makes a significant contribution to the changes of hepatoma cells metastasis.

journal_name

Eur J Med Res

journal_title

European journal of medical research

authors

Li T,Zhao S,Song B,Wei Z,Lu G,Zhou J,Huo T

doi

10.1186/s40001-015-0144-2

subject

Has Abstract

pub_date

2015-05-24 00:00:00

pages

eissn

0949-2321

issn

2047-783X

pii

10.1186/s40001-015-0144-2

journal_volume

pub_type

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