血管生长抑素基因抑制胰腺癌裸鼠移植瘤血管生成的实验研究

Inhibitory effects of angiostatin on angiogenesis of transplanted human pancreatic carcinoma in nude mice

目的:探讨人血管生长抑素基因对胰腺癌裸鼠移植瘤生长及血管生成的影响。方法:建立人胰腺癌细胞株BXPC-3裸鼠移植瘤模型,应用人血管生长抑素基因质粒转染胰腺癌裸鼠移植瘤,观察移植瘤生长情况。采用免疫组织化学技术检测肿瘤血管内皮生长因子(VEGF)表达情况和微血管密度(MVD)差异,透射电子显微镜观察肿瘤细胞情况。结果:治疗组肿瘤体积明显小于空白对照组和空质粒组(P<0.01),VEGF主要表达在肿瘤细胞的胞质内,治疗组、空白对照组和空质粒组平均灰度分别为179.57±5.22、150.87±3.44和163.40±3.54;阳性单位分别为14.94±2.26、31.26±2.72和29.21±2.95;MVD分别为10.60±74.56、19.33±2.52和18.67±5.29,治疗组与空白对照组和空质粒组比较,差异有统计学意义(P均<0.05)。电子显微镜下治疗组可见大量肿瘤细胞坏死。结论:人血管生长抑素基因能明显抑制胰腺癌裸鼠移植瘤血管生成,促进肿瘤细胞坏死,进而抑制肿瘤生长。

Objective： To explore the inhibitory effects of angiostatin on growth and angiogen- esis of transplanted human pancreatic carcinoma in nude mice. Methodst The animal model of transplanted human pancreatic carcinoma cell ing plasmid were transfected to the BXPC-3 ine BXPC-3 was established. The angiosatin express- cells tumor xengrafts of nude mice. The inhibitory onthe growth of tumor xengrafts was investigated. The expression of VEGF was detedted by immuno- histochemisty, and microvascular density（MVD） was investigated. The BXPC-3 cells were observed by transmission electron microscope（TEM）. Results： The volume of tumor xengrafts in therapy group were significant smaller than blank group and control vector group（P〈0.01 ）. VEGF main ex- pressed in cytoplasm, and the average gray of three groups was 179.57 ± 5.22, 150.87 ± 3.44 and 163.40 ± 3.54, and the postive unit of three groups was 14.94 ± 2.26, 31.26 ± 2.72 and 29.21 ± 2.95, and MVD of three groups was 10.60 ± 74.56, 19.33 ± 2.52 and 18.67 ± 5.29, respectively. The above data was significant statistic difference. The necrosis of many tumor cells was observed by TEM in therapy group. Conclusion： The inhibitory effect of angiostatin on angiogenesis of transplanted human pancreatic carcinoma in nude mice was significant, and resulted in cell necrosis and growth inhibited.