目的: 探讨血管内皮生长因子（vascular endothelial growth factor， VEGF）反义寡核苷酸对C57BL/6小鼠肺癌细胞的抑制作用。方法: 制作C57BL/6小鼠皮下肺癌模型40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、VEGF错义寡核苷酸（MODN）治疗组及对照组。接种Lewis肺癌细胞后24 h内，用ASODN、SODN及MODN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以及组织形态学改变，标本常规石蜡切片，H-E染色，用免疫组化方法检测VEGF蛋白表达。结果: 对照组、ASODN组、SODN组、MODN组平均瘤重分别为（7.33±0.71）g、（4.56±0.38）g、(7.59±0.32)g和（7.62±0.39）g，ASODN组、SODN组、MODN组抑瘤率分别为43.8%、5.5%、3.1%。光镜下观察, VEGF-ASODN 能明显抑制肿瘤细胞生长，降低增殖活性。 免疫组化结果表明,ASODN组VEGF的表达水平明显低于SODN组、MODN组及对照组（P<0.05）。CD34免疫组化结果表明，ASODN组MVD为8.25±2.12，与对照组(14.78±3.51)、SODN组(13.71±3.62)及MODN组(12.81±2.56)比较，ASODN组MVD明显减少（P<0.01）。结论: 原位注射VEGF反义寡核苷酸能抑制小鼠肺癌生长。

Objective: To study the inhibitory effect of VEGF antisense oligonucleotides (ASODN) on growth of Lewis lung cancer in C57BL/6 mice.Methods: Lewis lung cancer cells were cultured and implanted subcutaneously into 40 C57BL/6 mice, which were then divided into 4 groups: VEGF-ASODN treatment group, VEGF-SODN treatment group, BEGF-MODN treatment,and control group (normal saline). Mice in different groups were treated 24 hours after cell inoculation. The weight and volume of subcutaneous tumors was measured and the morphological changes of tumor cells was observed under microscope. VEGF protein and microvessel density were examined by immunohistochemistry.Partial tumor tissues were kept in liguid nitrogon.Results: The average tumor weights of the control, VEGF-ASODN, VEGF-SODN and VEGF-MODN groups were (7.33±0.71)g, (4.56±0.38) g, (7.59±0.32) g, and (7.62±0.39) g, respectively. The inhibition rates of tumor growth in VEGF-ASODN, VEGF-SODN and VEGF-MODN group were 43.8%, 5.5% and 3.1%, respectively. VEGF-ASPODN obviously inhibited the tumor cell growth and decelerated the tumor cell proliferation. Immunohistochemistry results showed that the expression of VEGF in ASODN group was remarkly lower than those in SODN group, MODN group and control group (P<0.05). The microvessels density (MVD) in the VEGF-ASODN, control, VEGF-SODN, and VEGF-MODN group were 8.25±2.12, 14.78±3.51, 13.71±3.62, and 12.81±2.56, respectively,with that of VEGF-ASODN remarkly lower than those of other groups（P<0.01）.Conclusion:Lewis lung cancer cells can be inhibited by the VEGF antisense oligonucleotides inoculated into tumor in the C57BL/6 mice.

黑龙江省“九五”攻关课题资助项目(GDDC190402)