重组人血管内皮生长抑制因子对人肺腺癌裸鼠移植瘤的放射效应影响

The Effects of Radiation Effects of rhVEGI-192 for Human Lung Adenocarcinoma Nude Mouse Transplantation Tumor

目的:探讨重组人血管内皮抑制因子(recombinant human vascular endothelial growth inhiloitor-192,rhVEGI-192)对人肺腺癌裸鼠移植瘤的放射增敏作用。方法:采用原核表达rhVEGI-192,获得目的蛋白。通过肿瘤倍增时间,计算药物的增敏系数。通过建立人肺腺癌裸鼠移植瘤模型,荷瘤裸鼠随机分为4组:对照组、10Gy、rhVEGI-192、rhVEGI-192+10Gy。采用6MV-X线进行照射,照射剂量为10Gy。获得移植瘤标本,利用免疫印迹法检测移植瘤中VEGF(vascular endothelial growth factor)的表达变化。结果:SDS电泳结果显示,目的蛋白位于22k D左右。10Gy照射时,重组人血管内皮抑制因子的EF(enhancement factor)值为1.5。和空白对照组相比,rhVEGI-192组和10Gy组移植瘤的生长受到抑制(P<0.001),rhVEGI-192+10Gy组移植瘤生长显著抑制(P<0.001),rhVEGI-192+10Gy组移植瘤较10Gy组有明显生长抑制。和空白组相比,rhVEGI-192组VEGF表达减少,而10Gy组VEGF表达变化不明显,rhVEGI-192+10Gy组VEGF表达明显减少。rhVEGI-192+10Gy和rhVEGI-192组相比,VEGF表达减少。结论:rhVEGI-192联合照射能够减少VEGF的表达。这可能是rhVEGI-192的增敏机制之一。

Objective： To evaluate the mechanism of radiosensitivity of rhVEGI-192 on human lung adenocarcinoma grafted in nude mice. Methods： Tumor-bearing model was established by injecting 973 cells to nude mice. Mice bearing tumor were randomly divided into four groups： control group,rhVEGI-192 group,radiation group,rhVEGI-192 ＋10 Gy group. In radiation group,mice were treated with 6 MV X-ray on the tumor. A dose of 10 Gy was applied. VEGF which expressed in tumor are detected by western blot. Results： EF of rhVEGI-192 ＋ 10 Gy group were 1. 5. Compared with control group,tumor growth in rhVEGI-192 group and 10 Gy group was inhibited（ P 0. 001）,tumor growth in rhVEGI-192 group ＋ 10 Gy group was inhibited significantly（ P 0. 001）. Compared with 10 Gy group,tumor growth in rhVEGI-192 ＋ 10 Gy group was inhibited significantly（ P 0. 001）. Compared with control group,VEGF level were decreased in rhVEGI-192 group,rhVEGI-192 ＋ 10 Gy group.VEGF level were the same with 10 Gy group. Compared with rhVEGI-192 group,VEGF level was decreased in rhVEGI-192＋ 10 Gy group. Conclusion： rhVEGI-192 ＋ radiation can decrease mouse tumor VEGF level,down-regulation VEGF is the radioenhancement mechanism of rhVEGI-192.