Avastin对神经母细胞瘤株SK-N-SH增殖影响的体外研究  

Effect of avastin on neuroblastoma SK-N-SH cell proliferation

作　　者：王智辉[1] 孙晓非[1] 甄子俊[1] 夏奕[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,中山大学肿瘤防治中心内科,广州510060

出　　处：《中华小儿外科杂志》2008年第2期110-113,共4页Chinese Journal of Pediatric Surgery

摘　　要：目的以人神经母细胞瘤SK-N-SH细胞株为研究对象探讨Avastin对其增殖的影响及可能机制。方法测定不同Avastin浓度对SK-N-SH细胞上清液VEGF水平的影响，对该株细胞的细胞毒作用及对其细胞周期及凋亡的影响。结果随着Avastin浓度升高，细胞上清液中游离VEGF水平逐渐下降；在一定剂量范围内，Avastin对该株细胞无明显细胞毒性作用；不同浓度Avastin作用于该株细胞，呈时间依赖性，影响细胞周期分布。结论Avastin可中和SK-N-SH细胞分泌的VEGF，无明显细胞毒性作用，但可影响细胞周期分布，提示Avastin与化疗药物联合应用可能有协同作用。Objective Vascular endothelial growth factor （VEGF） is associated with tumor growth and metastasis and is over-expressed in neuroblastoma. Avastin is the monoclonal antibody of VEGF and can inhibit tumor growth by blocking the VEGF signaling pathway. However, the mechanism remains unclear. The current study aims to assess the effect of Avastin on proliferation of human NB SK-N-SH cells. Methods ELISA was used to assay the expression of VEGF in supernatant of SK-N-SH cells. MTT assay was used to measure Avastin-induced cytotoxicity in SK-N-SH cells. Flow cytometry was used to detect the effect of Avastin on cell cycle and apoptosis. Results Avastin could neutralize VEGF and gradually decreased the level of VEGF in supernatant in SK-N-SH cells at increased concentrations. The level of VEGF was reduced to 0 μg/ml by Avastin at 50 μg/ml. Avastin did not induce cytotoxicity in SK-N-SH cells at 0. 5 μg/ml-50 μg/ml. Avastin at different concentrations induced cell cycle redistribution in a time-dependent manner. Avastin decreased the fraction of cells in G0-G1 phase and increased that in S phase at 5 μg/ml and 10 μg/ml. It also induced apoptosis at 50 μg/ml. Conclusions Avastin could neutralize the secreted VEGF, redistributes cells from G0-G1 phase to S phase and induces apoptosis in SK-N-SH cells. Avastin may be used as adjunct to chemotherapy of neuroblastoma.

关 键 词：神经母细胞瘤 血管内皮细胞生长因子 细胞增殖 

分 类 号：R739.4[医药卫生—肿瘤]