High-Dose and Long-Term Therapy With Interferon-Alfa Inhibits Tumor Growth and Recurrence in Nude Mice Bearing Human Hepatocellular Carcinoma Xenografts With High Metastatic Potential

• Published in: Hepatology (Baltimore, Md.) Vol. 32; no. 1; pp. 43 - 48
• Main Authors: Wang, Lu, Tang, Zhao-You, Qin, Lun-Xiu, Wu, Xiao-Feng, Sun, Hui-Chuan, Xue, Qiong, Ye, Sheng-Long
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Elsevier Inc 01.07.2000; Wiley
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Endothelium, Corneal - drug effects; Endothelium, Corneal - physiology; Humans; Immunomodulators; Interferon-alpha - therapeutic use; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Metastasis; Neoplasm Recurrence, Local - drug therapy; Neoplasm Transplantation; Pharmacology. Drug treatments; Transplantation, Heterologous; Tumor Cells, Cultured; Recurrence; Alpha interferon; Rodentia; Hepatic disease; Hepatocellular carcinoma; Malignant tumor; Metastasis; Potential; Heterograft; Long term; Immunomodulator; Vertebrata; Chemotherapy; Mammalia; Mouse; Animal; Antiviral; Digestive diseases; Tumor; Inhibition; Therapeutic protocol; High dose
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1053/jhep.2000.8525

Postoperative recurrence of human hepatocellular carcinoma (HCC) is the major issue that must be addressed to further improve prognosis. This study was undertaken to investigate the effects of interferon-alfa-1b (IFN-α-1b) on recurrent tumor and metastasis after curative resection in nude mice bearing an HCC xenograft with high metastatic potential. Tumor tissues from LCI-D20, a metastatic model of HCC in nude mice, were orthotopically implanted in 105 nude mice. Eleven days later, 64 mice underwent curative resection of liver tumors. IFN-α at different doses was administered subcutaneously to mice with or without resection. In mice without resection, when comparison was made among control, IFN 7.5 × 106 U/kg/day, 1.5 × 107 U/kg/day for treated groups, and 3 × 107 U/kg/day; tumor volume was 8,475 mm3 ± 2,636 mm3, 7,963 mm3 ± 3,214 mm3, 769 mm3 ± 287 mm3, and 13 mm3 ± 9 mm3; incidence of lung metastasis being 100%, 80%, 40%, and 0%; life span was 45 ± 4 days, 53 ± 8 days, 81 ± 6 days, and 105 ± 24 days, respectively. In mice with curative resection, when comparison was made among control, IFN 5 × 105 U/kg/day, 1 × 106 U/kg/day, 4 × 106 U/kg/day, 7.5 × 106 U/kg/day, 1.5 × 107 U/kg/day, and 3 × 107 U/kg/day for treated groups; incidence of recurrent tumor was 100%, 100%, 87.5%, 100%, 87.5%, 62.5%, and 12.5%; lung metastasis being 100%, 75%, 87.5%, 50%, 62.5%, 0%, and 0%, respectively. IFN-α inhibited neovascularization induced by LCI-D20 tumor specimens implanted into the micropocket of nude mice corneas. In conclusion, high-dose and long-term therapy with IFN-α dose-dependently inhibits tumor growth and recurrence after resection of HCC. The effect of IFN-α may be attributed to antiangiogenesis in this experiment. These results provide potential clinical implication, particularly for the prevention of recurrence after curative resection of HCC. (Hepatology 2000;32:43-48.)