重组人血管内皮抑制素联合贝伐珠单抗体内抑瘤作用的效果及分析  

Combining Bevacizumab with Endostatin Gets Better Antitumor Efficacy in Vivo in Lung Cancer Animal Model

作　　者：牛牛[1,2] 李宝兰[1,2] 刘朝阳 胡瑛[1,2] 李雪冰[1,2] 李杰[1,2] 史鹤龄[1,2] 张海清[4] 

机构地区：[1]北京市结核病胸部肿瘤研究所 [2]首都医科大学附属北京胸科医院综合科,北京101149 [3]中国医学科学院肿瘤研究所生物检测中心,北京100021 [4]首都医科大学附属北京胸科医院病理科,北京101149

出　　处：《中国肺癌杂志》2013年第2期61-66,共6页Chinese Journal of Lung Cancer

摘　　要：背景与目的研究重组人血管内皮抑制素和贝伐珠单抗在体内对肺腺癌抑制作用的差别及联合用药的效果。方法首先建立A549肺腺癌细胞系的荷瘤Balb/c小鼠动物模型,然后将小鼠随机分为4组,对照组使用普通生理盐水每日瘤周注射。重组人血管内皮抑制素治疗组使用重组人血管内皮抑素(3mg/kg)每日瘤周注射连续16天贝伐珠单抗治疗组使用贝伐珠单抗(5mg/kg)每周两次瘤周注射给药。贝伐珠单抗、重组人血管内皮抑制素联合用药组使用贝伐珠单抗(5mg/kg)每周两次瘤周注射给药+重组人血管内皮抑素(3mg/kg)每日瘤周注射给药。治疗16天后处死所有实验鼠切取肿瘤标本比较实体瘤大小,采用Westernblot的方法检测血管内皮生长因子A和C(vascularendothelialgrowthfactor/VEGF-A,C)在各组表达情况的差异。结果重组人血管内皮抑制素和贝伐珠单抗在体内实验中均表现出了抑制肿瘤生长的作用,贝伐珠单抗作用更加明显(52.36%vs38.68%)。联合使用可获得更好的效果(64.15%)。贝伐珠单抗只对VEGF-A有抑制作用(60.8%),重组人血管内皮抑制素对VEGF-A/C都有抑制作用(14.6%,30.3%)。联合用药组对VEGF-A/C的抑制作用最强(79.4%,44.2%)。结论重组人血管内皮抑制素和贝伐珠单抗都在裸鼠动物模型试验中表现出了明显的抑瘤效果,联合使用抑制肿瘤效果更加明显。恩度对肿瘤组织内VEGF-A/C都表现出了抑制作用贝伐珠单抗对VEGF-A表现出了较明显的抑制作用联合用药组对VEGF-A/C抑制作用更加明显。Background and objective The aim of this study is to investigate difference of antiangiogenesis ablility and interaction about bevacizumab and endostatin in vivo in lung cancer animal model. Methods First, we construct aBalb/c mice model with A549 lung adenocarcinoma cell. Then, we divide the mice into four groups randomly. Every group has six mice. Control group： mice injected with normal saline every day aroud the tumor. Endostatin group： mice injectedwith endostatin （Recombinant endostatin） injection （3 mg/kg） every day Peritumoral. Bevacizumab group： mice injected with bevacizumab twice a week （biw/S mg/kg） Peritumoral. Combing group： mice were injected with endostatin andbevacizumab （dose just like single drug group）. After 16 days, we executed mice and got the tumor tissue for next analysis. Results Based on this experiment, we found bevacizumab and endostatin expressed the ability for inhibiting tumor growthin vivo. Bevacizumab was more powerful （52.36% vs 38.68%）. Combining bevacizumab with endostatin could get better results （64.15%） than single drug did. Bevacizumab played the role by inhibiting VEGF-A expression （60.8%）. Endostatintook effect by inhibiting VEGF-A/C （14.6%, 30.3%）. Combining group present better antitumor efficacy than any single drug group did. （79.7%, 44.2%）. Conclusion Both bevacizumab and endostatin present the antiangiogenesis ability in vivoof lung cancer animal model. In our test, bevacizumab show better ability in inhibiting tumor growth than endostatin does. Additional, combing bevacizumab with endostatin reveal better potential to inhibit tumor growth than single drug does.

关 键 词：肺肿瘤 抗血管治疗 重组人血管内皮抑制素 贝伐珠单抗 

分 类 号：R734.2[医药卫生—肿瘤]