反义VEGF基因及内皮抑素基因转染对人巨细胞肺癌生物学行为的影响  

Inhibitory effect of antisense VEGF_(121) and endostatin genes transfection on tumor growth and metastasis of human giant cell lung cancer

作　　者：吴晓[1] 郑杰[1] 朱建健[1] 付坚[1] 马春树[1] 由江峰[1] 崔湘琳[1] 王洁良[1] 方伟岗[1] 周爱儒[1] 汤健[1] 吴秉铨[1] 

机构地区：[1]北京大学医学部病理学系,100083

出　　处：《中国肺癌杂志》2001年第2期83-87,共5页Chinese Journal of Lung Cancer

摘　　要：目的　探讨反义VEGF基因和内皮抑素基因联合转染在抑制肿瘤血管生成和肿瘤生长转移中的作用。方法　反义VEGF12 1cDNA脂质体法转染人肺巨细胞癌细胞 (PG AS VEGF) ,先行转基因细胞裸鼠异种移植 ,之后电脉冲介导PsectagA 内皮抑素基因转染 ,观察反义VEGF基因和内皮抑素转染对肿瘤血管生成和肿瘤生长转移的调节作用。结果　肿瘤内微血管密度在PG AS VEGF、转染空载体组分别为 40 .6 7± 9.35和5 8.34± 10 .5 2 (P <0 .0 5 ) ;裸鼠体内接种PG AS VEGF细胞后 18天 ,PG AS VEGF、转染空载体组肿瘤体积分别为 (0 .9779± 0 .2 42 1)和 (1.5 2 10± 0 .415 0 )cm3(P <0 .0 5 ) ;PG AS VEGF、转染空载体组淋巴结转移率分别为16 .7% (2 /12 )和 5 0 % (6 /12 ) (P <0 .0 5 )。在肿瘤局部行PsectagA 内皮抑素基因转染的PG AS VEGF瘤 ,当肿瘤生长到 2 1天时 ,肿瘤生长受到明显抑制 ,PsectagA 内皮抑素基因转染组与PsectagA空载体转染组肿瘤体积分别为 (1.5 889± 1.1396 )和 (3 .398± 2 .6 42 )cm3(P <0 .0 5 ) ;两者肿瘤淋巴结转移率分别为 12 .5 % (1/8)和 75 %(6 /8) (P <0 .0 5 )。结论　内皮抑素基因转染对反义VEGF基因转染的PG细胞裸鼠体内生长和淋巴结自发性转移有协同抑制作用。Objective To explore the co operative inhibitory effect of antisense VEGF gene and endostatin gene transfection on tumor angiogenesis, tumor growth and metastasis of lung cancer. Methods Antisense VEGF 121 cDNA was transfected into PG cells(PG AS VEGF) by lipofectin. After PG AS VEGF cells were xenografted to nude mice, PsectagA endostatin gene was transfected into nude mice by electric pulse mediation. The MVDs in tumors and tumor biological characteristics were observed. Results ①The MVD in PG AS VEGF tumor in nude mice was significantly lower than that in PG vector tumor (PG AS VEGF and PG vector: 40.67±9.35 and 58.34±10.52, respectively) in nude mice. ②There was no significant difference between the PG vector tumor and PG AS VEGF tumor in early stage of the tumor growth in vivo. However, PG AS VEGF tumor grew significantly more slowly than PG vector tumor after 18 days (P<0.05). ③PG AS VEGF tumor could lead to regional and/or distant lymph node metastases (16.7%, 2/12), which was much more infrequent than that in PG vector group (50%, 6/12). ④ PG AS VEGF tumor growth was remarkably inhibited by endostatin gene transfected at site of the tumor inoculation as compared with the control group in nude mice (P<0.05). ⑤The PG AS VEGF tumors transfected with the endostatin gene at site of the tumor inoculation(AST) could also produce much lower regional and/or distant lymph node metastases rate (12.5%, 1/8) than that in the PG AS VEGF tumor transfected with the PsectagA vector (ASP)(75%, 6/8). Conclusion Endostatin gene transfection could cooperatively inhibit the growth and spontaneous lymph node metastasis of antisense VEGF gene transfected PG cells in nude mice.

关 键 词：肺肿瘤 血管内皮生长因子 内皮抑素 基因转染 

分 类 号：R734.2[医药卫生—肿瘤]