抗肿瘤血管形成剂抑制肝癌生长及转移的实验研究  

An experimental study on effects of interferon α on growth and metastasis of hepatocellular carcinoma in nude mice

作　　者：王鲁[1] 汤钊猷[1] 孙惠川[1] 钦伦秀[1] 纪元[1] 薛琼[1] 吴志全[1] 刘银坤[1] 叶胜龙[1] 

机构地区：[1]复旦大学肝癌研究所肝外科,复旦大学中山医院,上海市200032

出　　处：《中华肝胆外科杂志》2002年第12期723-727,共5页Chinese Journal of Hepatobiliary Surgery

基　　金：本课题受上海市医学领先学科基金 ( 9830 0 1);美国中华医学会基金会基金 ( 93 5 83);国家重点基础研究规划项目子课题 (恶性肿瘤 )基金 (G19980 5 12 11)资助

摘　　要：目的　研究α干扰素 (IFN α)对肝癌生长及转移的抑制作用及其是否通过抑制一氧化氮合酶 (Ⅱ型 ,iNOS)和血管内皮生长因子 (VEGF)进而减少肝癌血管形成起作用。方法　应用裸鼠人肝癌转移模型LCI D2 0 ,于肿瘤移植后第 2天每只开始皮下注射不同剂量IFN α(3× 10 5U/d ,6×10 5U/d) ,每天 1次 ,对照组注射相同体积的生理盐水。每组治疗 35d后处死部分裸鼠 ,测量移植瘤大小 ,观察肺转移情况 ;剩余裸鼠继续用药观察IFN α对其生存时间的影响。LCI D2 0肿瘤组织移植到裸鼠角膜建立角膜微囊移植模型 ,检测IFN α对肝癌肿瘤血管形成的抑制作用。免疫组织化学方法检测治疗前后肝癌组织iNOS ,VEGF及肿瘤微血管密度变化。结果　对照组裸鼠肺转移率为10 0 % (10 /10 ) ,移植瘤大小为 8475± 2 6 36mm3,生存时间为 45± 4d ;IFN α 3× 10 5U/d治疗组分别为 5 0 % (4/8)、76 9± 2 87mm3 和 81± 6d ,与对照组比较移植瘤大小及生存时间差别有统计学意义 (P<0 0 1) ;而二者之间肺转移率无统计学差别 (P >0 0 5 ) ;IFN α 6× 10 5U/d治疗组则分别为 0 (0 /8)、13± 9mm3 和 10 5± 2 4d ,与对照组比较差别有统计学意义 (P <0 0 1)。应用裸鼠角膜微囊移植模型检测LCI D2Objective To investigate the effects of systemic administration of interferon α (INF-α) on the growth and metastasis of hepatocellular carcinoma (HCC) in BALB/c nude mice and determine whether IFN-α can inhibit the expression of induce nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) to reduce HCC angiogenesis. Methods Small pieces of tumor tissues from metastatic model of human HCC in nude mice (LCI-D20) were implanted into the liver of nude mice. IFN-α was administered s.c. at doses of 3×105 U/mice and 6×105 U/mice every day. The same volume of normal saline (NS) was injected into the controls. Part of the nude mice in each group were sacrificed 37 days later. At necropsy, the implanted tumor volume and lung metastasis were evaluated in both the treated and control groups. The left nude mice in each group were employed to determine whether IFN-α can prolong the life span. The antiangiogenic effects of IFN-α were tested after the tumor specimens of LCI-D20 model were implanted into micropocket of the corneas of nude mice. Meanwhile, the expression of iNOS, VEFG and MVD were detected with immunohistochemistry in both groups. Results The lung metastatic rate, implanted tumor size and life span were 100% (10/10), 8 475±2 636 mm3, 45±4 days respectively, whereas they were 50% (4/8), 769±287 mm3 (P<0.01) and 81±6 days (P<0.01) in the INF-α 3×105 U/day treated group (P<0.01);0 (0/8), 13±9 mm3, 105±24 days in the IFN-α 6×105 U/day treated group (P<0.01). Tumor specimens of LCI-D20 model strongly induced angiogenesis in the mice cornea and IFN-α inhibited this angiogenesis. The expression of VEGF was significantly higher in the control group than in the treated one (P<0.05). The MVD in the control group, INF-( 3(105 U/day treated group and IFN-α 6×105 U/day treated group was 114±18/HP, 66±5/HP and 21±9/HP, respectively (P<0.01). Conclusions IFN-α can inhibit the growth and metastasis of human HCC in nude mice in an dose-dependent manner, which might be due to ant

关 键 词：Α干扰素 肿瘤转移 实验研究 肝癌 抗肿瘤血管形成剂 

分 类 号：R735.7[医药卫生—肿瘤] R730.[医药卫生—临床医学]