pEGFP-ING4抑制裸鼠皮下人U87移植瘤生长及肿瘤血管生成

The inhibitory effects of pEGFP-ING4 on growth and angiogenesis of human glioma U87 cell xenografts in nude mice

目的探讨pEGFP-ING4对裸鼠体内人U87细胞移植瘤生长及对肿瘤血管生成的影响。方法将成功构建的18只人U87细胞裸鼠皮下移植瘤模型,随机分为pEGFP-ING4和pEGFP-C2转染组及PBS空白对照组3组,测量各组肿瘤的体积变化,荧光显微镜观察转染瘤体内绿色荧光蛋白(green fluorescent protein,GFP)的表达情况,免疫组织化学SABC法检测微血管密度(microvessel density,MVD)。结果荧光显微镜下pEGFP-ING4组和pEGFP-C2组均观察到GFP表达,接种后第21d、28d、35d各组皮下肿瘤体积(mm3)为:PBS组(201.8±19.3,418.9±26.4,622.1±51.3),pEGFP-C2组(197.6±18.9,398.4±20.4,593.7±48.7),pEGFP-ING4组(138.9±8.4,198.7±21.5,293.2±31.6),肿瘤接种后在同一时间点内,pEGFP-ING4组肿瘤体积明显小于另外两组(P<0.05);MVD检测(个/mm2):PBS组(15.83±0.98),pEGFP-C2组(15.83±1.62),pEGFP-ING4组(4.17±1.17),与另外两组比较,pEGFP-ING4组MVD明显降低(P<0.01)。结论 ING4基因能够明显抑制人U87细胞裸鼠皮下移植瘤的生长,抑制胶质瘤血管的生成可能是其抗肿瘤的重要机理之一。

Objective To study the effects of pEGFP - ING4 on the growth and angiogenesis of human U87 cells xenografts in nude mice. Methods The xenografts derived from U87 cells were established in 18 BALB/C nude mice. In- oculated mice were randomly divided into 3 groups： pEGFP - ING4, pEGFP - C2 and PBS groups. Tumor volume was measured and microvessel density （MVD） were detected using SABC immunohistochemistry. The expression of green fluorescent protein （GFP） was detected using a fluorescent microscope. Results GFP could be detected in pEGFP - ING4 and pEGFP- C2 groups but not in PBS group undermicroseope. After tumor inoculation, the 21th ,28 th ,35 th day the volume （ram3） of each group is ：PBS group（201.8 ± 19. 3,418. 9 ±26. 4 ,622. 1 ±51.3） ,pEGFP - C2 group（197. 6 ± 18.9 ,398.4 ±20. 4 ,593.7±48.7） ,pEGFP -ING4 group（138.9 ±8. 4 ,198.7 ±21.5,293.2 ±31.6）. Compared with the other two groups at the same time , pEGFP - ING4 group was suppressed significantly（ P 〈 0. 05 ）. The MVD was ： PBS group（15.83 ±0. 98） ,pEGFP - C2 group（ 15.83 ± 1.62）, pEGFP - ING4 group（4. 17 ±1.17） ,the MVD in pEGFP - ING4 group was significant reduction （P 〈 0. 01 ） compared with the other two groups. Conclusions ING4 gene can inhibit the growth of U87 cell xenografts in nude mouse. The inhibition of angiogenesis might play a key role in the antitumor effect of ING4.