Interferon alpha inhibits hepatocellular carcinoma growth through inducing apoptosis and interfering with adhesion of tumor endothelial cells.
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.
Zhang
Ti
T
Department of Hepatobiliary Surgery, Cancer Hospital of Tianjin Medical University, PR China.
Sun
Hui-Chuan
HC
Zhou
Hong-Yuan
HY
Luo
Jing-Tao
JT
Zhang
Bai-Lin
BL
Wang
Peng
P
Wang
Lu
L
Qin
Lun-Xiu
LX
Ren
Ning
N
Ye
Sheng-Long
SL
Li
Qiang
Q
Tang
Zhao-You
ZY
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016898:Interferon-alpha / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D020411:Oligonucleotide Array Sequence Analysis; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D016898:Interferon-alpha