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High‐lose and long‐term therapy with interferon‐alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential
Author(s) -
Wang Lu,
Tang ZhaoYou,
Qin LunXiu,
Wu XiaoFeng,
Sun HuiChuan,
Xue Qiong,
Ye ShengLong
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2000.8525
Subject(s) - medicine , hepatocellular carcinoma , metastasis , alpha interferon , gastroenterology , carcinoma , oncology , urology , interferon , cancer , immunology
Abstract 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 × 10 6 U/kg/day, 1.5 × 10 7 U/kg/day for treated groups, and 3 × 10 7 U/kg/day; tumor volume was 8,475 mm 3 ± 2,636 mm 3 , 7,963 mm 3 ± 3,214 mm 3 , 769 mm 3 ± 287 mm 3 , and 13 mm 3 ± 9 mm 3 ; 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 × 10 5 U/kg/day, 1 × 10 6 U/kg/day, 4 × 10 6 U/kg/day, 7.5 × 10 6 U/kg/day, 1.5 × 10 7 U/kg/day, and 3 × 10 7 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.