VEGF反义核酸对Lewis肺癌细胞作用的研究

Effects of VEGF antisense oligonudeotide on growth of Lewis lung cancer

目的探讨利用血管内皮生长因子(vascular endothelial growth factor,VEGF)反义寡核苷酸的基因治疗肺癌。方法制作C57 BL/小鼠皮下肺癌模型30只,分为VEGF反义寡核苷酸(ASODN)治疗组、VEGF正义寡核苷酸(SODN)治疗组及对照组。接种Lewis肺癌细胞后24h内,用ASODN及SODN皮下注射进行治疗,对照组只注射生理盐水,观察小鼠肿瘤的生长情况。用免疫组化方法检测VEGF蛋白表达,RT-PCR方法检测VEGF mRNA的表达。结果VEGF反义寡核苷酸治疗组、VEGF正义寡核苷酸治疗组、对照组平均瘤重分别为(4．31±0．45)g、(6．47±0．71)g、(6．23±0．76)g。VEGF反义寡核苷酸治疗组、VEGF正义寡核苷酸治疗组抑瘤率分别为41．8％、5．2％。VEGF反义寡核苷酸能明显抑制VEGF蛋白表达及VEGF mRNA的表达。结论原位注射VEGF反义寡核苷酸能抑制小鼠肺癌生长。

Objective To evaluate the gene therapy of lung cancer by vase,,lar endothelial growth factor （VEGF） antisense oligonucleotide（ASON）.Methods The lewis lung cancer cells were cultured and implanted subcutaneously into 30 C57BL/6 mice. These mice were divided into three groups： VEGF-ASODN group, VEGF-SODN group,and the control group. Gene therapy were given respectively 24 hours after lung cancer cell inoculation. The weight and volume of subcutaneous tumors were measured. VEGF protein was examined by immunohistocbemistry. Partial tumor tissues were put into the liquid nitrogen and VEGF mRNA were detected by RT-PCR.Results The tumor weights of the VEGF-ASPODN group, VEGF-SPODN group, and the control group were （4.31±0.45）g,（6.47±0.71）g, and （6.23±0.76）g, respectively.The inhibition rate of tumor growth of the VEGF-ASPODN group and VEGF- SPODN group were 42.7% and 5.9% respectively. VEGF- ASODN can inhibit the expression of VEGF protein and mRNA. Conclusion It is showed that the lewis lung cancer can be inhibited by the VEGF antisense oligonucleotide inoculated into the center of the tumor in the C57BL/6 mice.