肿瘤血管功能对Avastin联合环磷酰胺抗瘤效应的影响  

Correlation of Tumor Vessel Function to Synergistic Antitumor Effect of Avastin Combined Cyclophosphamide

作　　者：甄子俊[1] 何友兼[1] 孙晓非[1] 凌家瑜[1] 郑磊[1] 罗文标[1] 

机构地区：[1]华南肿瘤学国家重点实验室

出　　处：《癌症》2008年第4期354-358,共5页Chinese Journal of Cancer

摘　　要：背景与目的:肿瘤血管功能缺陷导致肿瘤间质压力高、缺氧及酸中毒,影响化疗药物的抗瘤作用。本研究观察Avastin治疗神经母细胞瘤(neuroblastoma,NB)后肿瘤血管功能的动态改变,并探讨此改变对Avastin联合环磷酰胺(cyclophosphamide,CPM)协同抗瘤效应的影响。方法:培养人NB细胞并接种于裸小鼠形成NB裸鼠移植瘤。由裸鼠尾静脉注入Avastin5mg/kg。于Avastin治疗后6h、第3天、第6天、第9天将裸鼠分批处死,用荧光素Hoechst33342标记法检测Avastin治疗后不同时点的肿瘤血管功能。将Avastin联合CPM治疗NB荷瘤裸鼠,比较于Avastin用药后第1天予CPM化疗(联合方案Ⅰ组)或于Avastin用药后肿瘤血管功能得到最大改善的时间点予CPM化疗(联合方案Ⅱ组)的抗瘤效应。结果:Avastin治疗后第6天肿瘤血管功能得到最大改善。用Avastin和/或CPM治疗NB裸鼠移植瘤3周后,Avastin单药治疗组、CPM单药化疗组、联合方案Ⅰ组、联合方案Ⅱ组的抑瘤率分别为36.4%、38.2%、55.9%、66.8%。Avastin与CPM联合给药时,在Avastin用药后的第6天比第1天予CPM化疗效果较好(P<0.05)。结论:利用Avastin治疗后肿瘤血管功能得到最大改善的时机,予以CPM化疗能增加Avastin与CPM的协同抗瘤作用。BACKGROUND ＆ OBJECTIVE.. Dysfunction of tumor vessels renders high interstitial pressure, hypoxia and acidosis, causing the barrier of cytotoxic efficacy of chemotherapeutic agents. This study was to observe the dynamic alteration of vessel function in neuroblastoma （NB） after treatment of Avastin, and explore the correlation of tumor vessel function to synergistic antitumor effect of Avastin plus cyclophosphamide （CPM）. METHODS. Human NB cells were incubated and transplanted into nude mice to form NB xenografts. Avastin at a dose of 5 mg/kg was administered to the mice through the tail veins. The mice were killed on the 6th hour, 3rd day, 6th day and 9th day after Avastin treatment, separately. Tumor vessel function was tested with fluorescein Hoechst33342 staining. NB-bearing mice were treated with Avastin plus CPM. The synergistic antitumor effects were compared when CPM was administered simultaneously with Avastin （combined regimen I ） or at the time the tumor vessel function was mostly improved after Avastin administration （combined regimen II ）. RESULTS. The tumor vessel function was mostly improved on the 6th day after Avastin treatment. Tumor inhibition rates were 36.4% in Avastin monotherapy group, 38.2% in CPM monotherapy group, 55.9% in combined regimen I group, and 66.8% in combined regimen II group at 3 weeks after treatment. The synergistic antitumor effect was better when CPM was administered on the 6th day after Avastin treatment as compared with it used simultaneously with Avastin （P〈0.05）. CONCLUSION： The synergistic antitumor effect can be augmented when CPM is administered at the time the tumor vessel function is mostly improved after Avastin treatment.

关 键 词：肿瘤 血管功能 AVASTIN 环磷酰胺 联合用药 

分 类 号：R730.5[医药卫生—肿瘤]