抗血管内皮生长因子抗体对肝癌的放射增敏作用
作者：郑青平,陈龙华,石玉生【关键词】 肝肿瘤;放射疗法;抗VEGF单抗;放射增敏
Radiosensibility of human hepatocellular carcinoma xenografts enhanced by antivascular endothelial growth factor monoclonal antibody
【Abstract】 AIM: To investigate the inhibiting effects of combining antivascular endothelial growth factor (VEGF) monoclonal antibody (mAb) therapy with radiotherapy on the growth of hepatocellular carcinoma xenografts in vivo. METHODS: Human hepatocellular carcinoma cell line, SMMC7721, was implanted sc in mice. The mice with xenografts were divided into 4 groups, radiation (RT) 20 Gy group, RT 20 Gy plus mAb group, RT 30 Gy plus mAb group and control group. AntiVEGF mAb was injected ip on alternate days for a total of 6 injections at a dosage of 50 μg/mouse. Single radiation doses were given 24 h after the 4th injection of mAb. Tumor diameters were measured and tumor volume was calculated. Mice were sacrificed 2 wk after the 6th injection and the intratumoral microvessel density was determined by counting the stained vessels with immunohistochemistry. RESULTS: Radiation significantly reduced the growth and the microvessel density of tumors. The inhibitory effects were more significant when radiation was combined with antiVEGF mAb, and RT 30 Gy plus mAb was more effective than RT 20 Gy plus mAb. For RT 20 Gy group, RT 20 Gy plus mAb group and RT 30 Gy plus mAb group, the inhibitory rates of tumor weight were 75.3%, 83.9% and 94.7%, respectively. CONCLUSION: AntiVEGF mAb enhances the radiosensibility of human hepatocellular carcinoma xenografts.The strategy is one of the approaches for hepatocellular carcinoma treatment.
【Keywords】 hepatocellular carcinoma; radiotherapy; antiVEGF mAb; radiosensibility
【摘要】 目的: 观察抗血管内皮生长因子抗体(VEGF mAb)与不同剂量放射联合对肝癌裸鼠移植瘤生长的抑制作用. 方法: 将SMMC7721肝癌细胞种植于裸鼠皮下,成瘤动物分为单纯放射20 Gy组、放射20 Gy 抗体组、放射30 Gy 抗体组和对照组,腹腔给予抗VEGF mAb 50 μg/只，隔日1次,共6次,放射剂量一次性给予.测量肿瘤直径并计算瘤体积,抗体给药结束后2 wk处死动物,免疫组化法测肿瘤微血管密度(MVD). 结果: 放射能抑制肿瘤生长,减少肿瘤MVD,放射与抗体结合对肿瘤生长的抑制作用更显著，且放射30 Gy 抗体比放射20 Gy 抗体效果更好.单纯放射20 Gy组、放射20 Gy 抗体组和放射30 Gy 抗体组的瘤质量抑制率分别为75.3%,83.9%和94.7%,差异有统计学意义. 结论: 抗VEGF mAb对放射治疗肝癌移植瘤有增敏作用,是肝癌综合治疗的有效途径之一.
【关键词】 肝肿瘤;放射疗法;抗VEGF单抗;放射增敏
0引言
放射治疗肿瘤的目的是尽可能提高肿瘤的放射剂量以杀灭瘤细胞,但同时正常组织和器官所受辐射量也相应提高,增加了放射治疗的副反应,因而限制了通过提高放射剂量来控制肿瘤的`作用.肝癌是放射欠敏感肿瘤,而正常肝组织对放射线较敏感.单纯放射治疗肝癌的疗效并不理想［1］.有报道［2］抗血管内皮生长因子(vascular endothelial growth factor, VEGF)抗体可以抑制肝癌裸鼠移植瘤生长,我们观察抗VEGF mAb与不同放射剂量联合对肝癌移植瘤生长的抑制作用,以了解两者联合应用的机制与方法.
1材料和方法
1.1材料Balb/cnu/nu小鼠20只(南方医科大学实验动物中心),5～
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