The effects of MIBG on the invasive properties of HepG2 hepatocellular carcinoma cells.

Yan Su, Xiao-Qin Guan, Feng-Qiu Liu, Ya-Lan Wang

Index: Int. J. Mol. Med. 34(3) , 842-8, (2014)

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Abstract

The aim of the present study was to investigate the effects of meta-iodobenzylguanidine (MIBG) on the invasive properties of hepatocellular carcinoma (HCC) cells and examine whether these effects are due to the ability of MIBG to inhibit arginine-specific mono-ADP-ribosylation. Samples from patients with HCC were divided into 2 groups, a metastatic group and a non-metastatic group. Immunohistochemistry and RT-PCR were used to detect the protein and mRNA expression of arginine-specific adenosine diphosphate-ribosyltransferase 1 (ART1) and integrin α7 in the HCC tissues. In addition, the expression of ART1 was measured in HepG2 HCC cells by immunofluorescence. The inhibition of the metastasis of HepG2 cells by MIBG at various concentrations was measured by MTT assay. In addition, the effects of MIBG on HepG2 cell metastasis were measured using a scratch wound assay and a transwell invasion assay. Western blot analysis was used to detect the protein expression of ART1, integrin α7, focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K) and urokinase-type plasminogen activator (uPA) in the HepG2 cells. The mRNA and protein levels of ART1 and integrin α7 were higher in the metastatic HCC samples than in the non-metastatic HCC samples. ART1 expression was detected in the HepG2 cells. The half maximal inhibition concentration (IC50) of MIBG in the HepG2 cells was 200 µmol/l (P<0.05). Within a certain dose range, MIBG exerted inhibitory effects on HepG2 cell migration in a dose-dependent manner. Treatment with MIBG significantly inhibited the migration and invasion of the HepG2 cells relative to the control cells (P<0.05) and reduced the protein expression of ART1, integrin α7, FAK, PI3K and uPA (P<0.05). Our data demonstrate that ART1 and integrin α7 may be involved in the invasive and metastatic properties of HCC cells. MIBG inhibited the migration and invasion of HepG2 cells, possibly through the inhibition of arginine-specific single-adenosine diphosphate ribosylation and the suppression of the protein expression of integrin α7β1, FAK and PI3K and the secretion of uPA, leading to reduced invasion by HepG2 cells.