Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells

Abstract 

The aim of this study was to observe the effect of interferon alpha (IFNα) on tumor endothelial cells (TECs) in highly metastatic hepatocellular carcinoma (HCC) model, and to investigate the underlying mechanism. Nude mice with HCC xenograft were treated with IFNα. Gene expression profiles of TECs were analyzed by utilizing cDNA microarray. The differentiation of tumor blood vessels was evaluated by CD31/αSMA dual immunohistochemistry. Apoptosis of TECs was determined by CD31/TUNEL double staining. The functions of TECs in adhesion and uptake of acetylated low-density lipoprotein were observed in vitro. Results showed that IFNα effectively inhibited HCC tumor growth, with decreased microvessel density, increased apoptosis in TECs and normalized tumor blood vessels. cDNA microarray analysis revealed differential gene expression patterns in TECs under the treatment of IFNα. The cell-cell contact distribution of VE-Cadherin and uptake of acetylated low-density lipoprotein were significantly inhibited by IFNα in cultivated TECs. These results suggest that IFNα may induce apoptosis and interfere with hemophilic adhesion of TECs. The changes of gene expression in TECs contribute essentially to its effect of anti-angiogenesis and the subsequent inhibition of tumor progression.

Abbreviations: HCC, hepatocellular carcinoma, IFNα, interferon alpha, TEC, tumor endothelial cell, DAPI, 4’,6-diamidino-2-phenylindole, PBS, phosphate buffered saline

Keywords: Hepatocellular carcinoma, Interferon alpha, Angiogenesis, Tumor endothelium