title: Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice.
abstract: The aim of this study was to examine the mechanism of interferon alpha (IFN-alpha) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-alpha was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136+/-794 mm(3)(mean+/-standard deviation), 100%, 265.7+/-154.7 pg/ml, and 144+/-37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89+/-45 mm(3), 12.5%, 53.3+/-9.9 pg/ml, and 86+/-25/HP, respectively, in the IFN-alpha 1.5 x 10(7)U/kg treatment group (P<0.05) and 26.7%, 46+/-21 mm(3), 0%, 65.2+/-17.9 pg/ml, and 39+/-14/HP in the IFN-alpha 3 x 10(7)U/kg treatment group, respectively (P<0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-alpha treatment groups. IFN-alpha inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, Peoples Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wu
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wu
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Kang-Da
authors.initials: KD
authors.lastname: Liu
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001363:Awards and Prizes; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000601:surgery; D013505:Digestive System Surgical Procedures; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D020033:Protein Isoforms / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012955:Societies, Medical; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D016898:Interferon-alpha; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2