Avastin联合环磷酰胺治疗神经母细胞瘤裸鼠移植瘤的研究

目的 探讨Avastin抗神经母细胞瘤(NB)裸鼠移植瘤生长的作用,以及对血清血管内皮生长因子(VEGF)水平的影响.方法 培养NB细胞并建立NB裸鼠移植瘤.用Avastin单药或与环磷酰胺(CPM)联合治疗NB裸鼠移植瘤.Avastin剂量为5 rag/kg,由尾静脉注入,每周1次;CPM75 mg/kg,仅1次.于第22天处死裸鼠,计算肿瘤体积及抑瘤率.应用抗CD34免疫组化法检测肿瘤微血管密度,ELISA法测定各组治疗结束后血清VEGF(sVEGF)水平.结果 Avastin单药治疗、CPM单药化疗、Avastin联合CPM治疗NB裸鼠移植瘤的抑瘤率分别是44.0%、38.1%、62.8%.Avastin联合CPM化疗与Avastin单药治疗和CPM单药化疗比较,差异均有统计学意义(P＜0.05).Avastin对NB血管生成的抑制率为64%.Avastin治疗后尽管裸鼠肿瘤已明显缩小,但sVEGF升高至对照组的1.9～2.4倍.结论 Avastin能抑制NB裸鼠移植瘤的生长,而且与CPM有协同抗NB作用.sVEGF不能用于监测Avastin抗瘤效果.

Anti-tumor effect of avustin for neuroblastoma xenografts

Objective To investigate the anti-tumor effect of avastin for neuroblastoma (NB)xenografts of mice and the influence on the serum vascular endothelial growth factor (sVEGF).Methods Human NB cells were incubated and transplanted to the nude mice to get the NB xenografts.NB mice were treated with avastin and/or cyclophosphamide (CPM).Avastin was administered to the mice via tail vein injection with a dose of 5 mg/kg once per week.CPM was administered with the single dose of 75 mg/kg.The mice were killed on the 22nd day after treatment.The tumor volume and inhibitory rate were observed.The tumor micro-vessel density was detected by anti-CD34 immunohistochemistry.The sVEGF was detected by ELISA.Results The tumor inhibitory rates of avastin,CPM,and avastin plus CPM regimen were 44.0%,38.1%,62.8% respectively.The tumor inhibitory rate of avastin plus CPM regimen was significantly higher than that of either avastin or CPM alone (P＜0.05).The NB angiogenesis was decreased to 64% by avastin.Though avastin caused significant regression of tumors,sVEGF was 1.9～2.4 times higher than that of control.Conclusions Avastin can inhibit the growth of NB xenografts and has the synergistic anti-tumor effect on NB when combined with CPM.