抗血管内皮生长因子抗体对实验性肝癌的生长抑制作用

The Growth Inhibition Effect of Antibody Against Vascular Endothelial Growth Factor on Experimental Hepatocellular Carcinoma in vivo

目的 了解抗血管内皮生长因子 (VEGF)抗体对人肝癌的生长抑制作用。方法 在已建立的人肝癌裸鼠皮下种植瘤的瘤灶旁 ,注射抗VEGF抗体 ,观察肿瘤生长情况 ,用CD3 1的免疫组化方法检测肿瘤内部的微血管密度(iMVD) ,用原位末端转移酶标记技术检测凋亡的肿瘤细胞。结果 实验结束后 1周 ,实验组和对照组肿瘤大小 (长×宽 )是 (2 6.46± 19.81)mm2 和 (10 5 .77± 17.40 )mm2 (P<0 .0 0 1) ,2周后是 (4 5 .2 0± 2 3 .0 2 )mm2 和 (15 0 .77± 77.41)mm2 (P<0 .0 5 ) ,而此时肿瘤的iMVD是 (2 3 11± 12 0 )个 /mm2 和 (3 90 0± 3 2 8)个 /mm2 (P<0 .0 0 1) ;肿瘤细胞凋亡指数是 15 .3 1%和 6.83 % (P<0 .0 0 5 )。结论 抗VEGF抗体能通过抑制肿瘤微血管的生长 ,抑制实验性人肝癌的生长 ,其实质是增加了肿瘤细胞凋亡。

Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). Methods The monoclonal anti VEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC 7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD 31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) assay. Results In the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm 2 vs (105.77±17.40) mm 2 ( P <0.001) and (45.20±23.02) mm 2 vs (150.77±77.41) mm 2 ( P <0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm 2 vs (3 900±328)/mm 2( P <0.001 ) and AI being (15.31% vs 6.83%), P <0.005. Conclusion The anti VEGF antibody can suppress the xenograft tumour growth of the human SMMC 7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.