血管内皮生长因子反义寡核苷酸治疗联合放射治疗可提高兔颌面部 VX2 肿瘤的疗效。

Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits.

机构信息

Department of Radiology, Shanghai First People's Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai, China.

出版信息

Eur J Radiol. 2011 May;78(2):272-6. doi: 10.1016/j.ejrad.2010.11.036. Epub 2010 Dec 28.

DOI:10.1016/j.ejrad.2010.11.036

PMID:21193276

Abstract

PURPOSE

To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits.

METHODS

We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 μg of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 μg of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 μl 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF.

RESULTS

In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05).

CONCLUSION

Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve as a reliable technique for in vivo monitoring.

摘要

目的

研究血管内皮生长因子（VEGF）反义寡核苷酸治疗联合放疗对兔颌面 VX2 肿瘤的影响。

方法

采用 24 只新西兰大白兔建立颌面 VX2 肿瘤模型，随机分为 4 组：放疗组（A 组），给予 16Gy 放疗；VEGF 反义寡核苷酸治疗组（B 组），于瘤内注射 150μg VEGF 反义寡核苷酸；VEGF 反义寡核苷酸联合放疗组（C 组），于 16Gy 放疗后即刻瘤内注射 150μg VEGF 反义寡核苷酸；对照组（D 组），于瘤内注射 300μl 5%葡萄糖水。治疗后第 3、14 天行动态对比增强磁共振成像（DCE-MRI）检查，计算最大增强率（MER）、斜率（SLE）和肿瘤体积变化。治疗后第 14 天处死动物取标本行病理检查及 VEGF 免疫组化染色。

结果

C 组治疗后第 14 天肿瘤体积明显缩小，与治疗前、治疗后第 3 天及其他各组比较差异均有统计学意义（P<0.01）；治疗后 MER、SLE 值均较治疗前降低，差异有统计学意义（P<0.05）。病理标本可见肿瘤细胞水肿、出血、坏死，血管壁增厚、管腔闭塞，VEGF 表达减少。C 组免疫组化评分（IHS）与 A、D 两组比较差异均有统计学意义（P<0.05）。