血管内皮生长因子反义基因转染对高转移人巨细胞肺癌细胞系生物学行为的影响  

Inhibition of growth and metastasis of human giant cell carcinoma of the lung by transfection of antisense VEGF121 cDNA

作　　者：吴晓[1] 郑杰[1] 付坚[1] 由江蜂 崔湘琳[1] 王洁良[1] 方伟岗[1] 周爱儒[1] 吴秉铨[1] 

机构地区：[1]北京大学医学部病理学系,100083

出　　处：《中华病理学杂志》2000年第5期363-366,共4页Chinese Journal of Pathology

基　　金：国家自然科学基金资助项目 !(396 0 0 0 5 7)

摘　　要：目的　探讨反义血管内皮生长因子 (VEGF)基因转染在抑制恶性肿瘤生长和转移的抗肿瘤血管基因治疗中的意义。方法　利用基因重组技术构建正义和反义VEGF12 1cDNA真核表达载体 ,用脂质体法转染高转移性人巨细胞肺癌细胞 (PG) ,经Northern杂交和Western印迹免疫化学检测VEGFmRNA和蛋白质的表达水平 ,并对转染前后细胞进行体外生长和裸鼠体内生长转移等多项生物学行为实验。结果　转染反义VEGF基因的细胞 3.3kbVEGFmRNA和相对分子质量为 45 0 0 0、410 0 0和 32 0 0 0蛋白质的表达水平降低 ,与对照组比较 ,裸鼠体内成瘤时间延长 ,肿瘤生长速度减慢 ,肿瘤在体内生长第 18d时 ,体积差异有显著性意义 (P <0 0 5 ) ;转移能力降低 ,淋巴结转移率差异有显著性意义 (P <0 0 5 )。Objective To explore the effects of blocking the VEGF/VEGF receptor paracrine pathway on growth and metastasis of human lung carcinoma cell line PG and to evaluate its potential application in gene therapy of cancer. Methods The eukaryotic expression vectors bearing either sense VEGF121 cDNA or antisense VEGF121 cDNA was constructed and transfected into PG cells. In vitro and in vivo tests such as Northern blotting hybridization, Western blotting immunochemistry analysis, as well as xenografting in nude mice were used to analyze the effect of antisense VEGF. Results The transfectants stably expressing antisense VEGF121 were observed to produce markedly reduced 3.3 kb VEGF mRNA and 45 KD、41 KD、32KD VEGF proteins. When xenografted s.c. into nude mice, growth and metastasis of the antisense VEGF transfected cell lines were greatly inhibited when compared with control cells. Conclusion Antisense VEGF gene significantly inhibited tumor growth and metastasis and may provide an experimental example for the development of antiangiogenic gene therapy.

关 键 词：肿瘤转移 VEGF 肺癌 基因转染 CDNA 

分 类 号：R734.2[医药卫生—肿瘤]