肝素在人肝癌裸鼠转移模型中对肿瘤生长转移的影响

ROLE OF HEPARIN ON TUMOR GROWTH AND METASTASIS IN MODEL OF HUMAN HEPATOCELLULAR CARCINOMA IN NUDE MICE

目的观察肝素对肝细胞癌(HCC)生物学特性的影响。方法构建裸鼠肝癌转移模型40例,分肝素、抑肽酶和止血芳酸干预治疗组、生理盐水对照组,比较肿瘤生长、转移和宿主生存。用免疫组化方法和酶活性检测方法,检测实验各组血浆和肿瘤组织中尿激酶型纤溶酶原激活物(uPA)和纤溶酶原激活物抑制剂(PAI-1)的变化。结果干预治疗30天肝素治疗组与对照组比较,肿瘤直径为1.50±0.61cm比2.98±0.50cm(P<0.001);肿瘤腹壁浸润率为20%比100%(P<0.05);肺转移率为20%比60%;50天生存率为60%比0。其他治疗组与对照组比较结果差异无显著性。免疫组化和 PAI-1活性检测结果表明:肝素治疗组肿瘤组织中 uPA 和 PAI-1阳性率低于对照组,PAI-1活性有降低趋势。结论在肝癌转移模型中,肝素有抑制肿瘤生长、抑制肿瘤浸润转移和提高宿主生存期的作用。

Objective To observe the role of heparin in biological behaviour of hepatocellular carcinoma(HCC).Methods 40 nude mice with LCI-D20 metastatic model of human HCC(MMHCC) were established.Heparin,aprotinin and aminomethylbenzoic acid were used for test to intervene HCC progression in MMHCC,and to compare with the saline control.The changes of plasminogen activator (uPA)and its inhibitor(PAI-1)were determined by PAl-1 activity kit and immunohistochemistry with monoclonal antibody against uPA and PAl-1.Results When the heparin-treated group was compared to the control group after treating for 30 days,tumor size was 1.50±0.61cm vs 2.98±0.50cm(P<0.001),tumor local invasion rate was 20% vs 100%(P<0.05),lung metastasis rate was 20% vs 60% and 50 days survival rate was 60% vs 0 respectively.Conclusion Our investigation suggested that heparin could not only inhibit tumor growth,but also inhibit tumor invasion and metastasis,and improve host survival in MMHCC.