Wang L, Tang Z Y, Qin L X, Wu X F, Sun H C, Xue Q, Ye S L
Liver Cancer Institute and Zhongshan Hospital, Shanghai Medical University, Shanghai, China.
Hepatology. 2000 Jul;32(1):43-8. 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-alpha-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-alpha 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 x 10(6) U/kg/day, 1.5 x 10(7) U/kg/day for treated groups, and 3 x 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 x 10(5) U/kg/day, 1 x 10(6) U/kg/day, 4 x 10(6) U/kg/day, 7.5 x 10(6) U/kg/day, 1.5 x 10(7) U/kg/day, and 3 x 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-alpha 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-alpha dose-dependently inhibits tumor growth and recurrence after resection of HCC. The effect of IFN-alpha 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.
人类肝细胞癌（HCC）术后复发是进一步改善预后必须解决的主要问题。本研究旨在探讨干扰素α-1b（IFN-α-1b）对具有高转移潜能的HCC裸鼠异种移植瘤根治性切除术后肿瘤复发和转移的影响。将来自裸鼠HCC转移模型LCI-D20的肿瘤组织原位植入105只裸鼠体内。11天后，64只小鼠接受了肝肿瘤的根治性切除。对有或无切除的小鼠皮下给予不同剂量的IFN-α。在未切除的小鼠中，对照组、IFN 7.5×10⁶U/kg/天、1.5×10⁷U/kg/天和3×10⁷U/kg/天治疗组之间比较；肿瘤体积分别为8475mm³±2636mm³、7963mm³±3214mm³、769mm³±287mm³和13mm³±9mm³；肺转移发生率分别为100%、80%、40%和0%；寿命分别为45±4天、53±8天、81±6天和105±24天。在根治性切除的小鼠中，对照组、IFN 5×10⁵U/kg/天、1×10⁶U/kg/天、4×10⁶U/kg/天、7.5×10⁶U/kg/天、1.5×10⁷U/kg/天和3×10⁷U/kg/天治疗组之间比较；肿瘤复发率分别为100%、100%、87.5%、100%、87.5%、62.5%和12.5%；肺转移发生率分别为100%、75%、87.5%、50%、62.5%、0%和0%。IFN-α抑制了植入裸鼠角膜微袋中的LCI-D20肿瘤标本诱导的新生血管形成。总之，高剂量和长期的IFN-α治疗剂量依赖性地抑制HCC切除术后的肿瘤生长和复发。在本实验中，IFN-α的作用可能归因于抗血管生成。这些结果具有潜在的临床意义，特别是对于预防HCC根治性切除术后的复发。
