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Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells.
- Source :
-
Cancer letters [Cancer Lett] 2010 Apr 28; Vol. 290 (2), pp. 204-10. Date of Electronic Publication: 2009 Oct 12. - Publication Year :
- 2010
-
Abstract
- The aim of this study was to observe the effect of interferon alpha (IFNalpha) 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 IFNalpha. Gene expression profiles of TECs were analyzed by utilizing cDNA microarray. The differentiation of tumor blood vessels was evaluated by CD31/alphaSMA 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 IFNalpha 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 IFNalpha. The cell-cell contact distribution of VE-Cadherin and uptake of acetylated low-density lipoprotein were significantly inhibited by IFNalpha in cultivated TECs. These results suggest that IFNalpha 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.<br /> (2009 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Carcinoma, Hepatocellular blood supply
Carcinoma, Hepatocellular pathology
Cell Adhesion drug effects
Cell Line, Tumor
Endothelial Cells drug effects
Fluorescent Antibody Technique
Gene Expression
Gene Expression Profiling
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Liver Neoplasms, Experimental blood supply
Liver Neoplasms, Experimental pathology
Male
Mice
Mice, Nude
Oligonucleotide Array Sequence Analysis
Xenograft Model Antitumor Assays
Angiogenesis Inhibitors pharmacology
Apoptosis drug effects
Carcinoma, Hepatocellular drug therapy
Interferon-alpha pharmacology
Liver Neoplasms, Experimental drug therapy
Neovascularization, Pathologic drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7980
- Volume :
- 290
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer letters
- Publication Type :
- Academic Journal
- Accession number :
- 19822391
- Full Text :
- https://doi.org/10.1016/j.canlet.2009.09.009