血管生成在Lewis肺癌生长转移过程中的作用

Effect of Angiogenesis on Growth and Metastasis of Lewis Lung Carcinoma

目的建立能够模拟肿瘤生长、侵袭转移动态全过程的动物模型,利用该模型探讨血管生成与肿瘤生长、转移的关系。方法Lewis肺癌(LLC)在C57BL/6小鼠体内连续传代,观察第2代(早期组)、第8代(中期组)和第15代(晚期组)荷瘤小鼠肿瘤生长和肺转移的情况,采用免疫组织化学法检测各组荷瘤小鼠肿瘤组织中血管内皮生长因子(VEGF)、缺氧诱导因子1α(HIF-1α)和微血管密度(MVD)的表达。结果(1)早、中、晚期三组小鼠肿瘤随传代次数的增加生长速度加快、侵袭力增强,肺转移率升高。(2)VEGF、HIF-1α和MVD在早、中、晚期三组小鼠瘤组织中的阳性表达均呈升高趋势,差别有统计学意义(P<0.05),且HIF-1α与VEGF、VEGF与MVD的表达均呈正相关。结论Lewis肺癌在小鼠体内连续传代过程中生长速度加快,转移潜能增强,而血管生成在这个动态过程中发挥了重要作用,使肿瘤得以持续生长和扩散转移。

Objective Establishing an animal model that can simulate the dynamic process of tumor progression and metastasis and to explore the important role of angiogenesis in tumor progression and metastasis by this model.Methods The Lewis lung carcinoma（LLC） was maintained by serial passage in C57BL/6 mice, to observe the dynamic process of tumor progression and metastasis of the second generation（the group of earlier stage）,the eighth generation（the group of intermediate stage） and the fifteenth generation（the group of advanced stage）, immunohistochemistry was used to detect the expression of HIF-1α、VEGF and MVD in tumors from each group.Results （1） With increasing numbers of passage, the tumor’s growth velocity speeded up, the invasive power was gradually enhanced and the rate of pulmonary metastasis increased. （2）The expression of HIF-1α,VEGF and MVD in tumors from the group of earlier stage、intermediate stage and advanced stage were different （P〈0.05）.What’s more, there was statistically significant correlation betweeen the expression of HIF-1α and VEGF;VEGF and MVD.Conclusion The growth velocity of LLC speeded up and the tumor′s metastasis potential was enhanced in the process of serial passage in mice,and angiogenesis played an important role in this dynamic process. As a result, tumor can keep on growing and developing pulmonary metastasis.