Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice.
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.
Wang
Lu
L
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, Peoples Republic of China.
Wu
Wei-Zhong
WZ
Sun
Hui-Chuan
HC
Wu
Xiao-Feng
XF
Qin
Lun-Xiu
LX
Liu
Yin-Kun
YK
Liu
Kang-Da
KD
Tang
Zhao-You
ZY
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
D020533:Angiogenesis Inhibitors; D016898:Interferon-alpha; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2