贝伐单抗联合化疗药物诱导白血病细胞株凋亡的实验研究  

Experimental study of apoptosis in leukemic cell lines induced by combined use of Bevacizumab and chemotherapeutic drug

作　　者：陈敬德[1] 韩颖[1] 郑伟萍[2] 黄滨滨[1] 薄兰君[1] 付建非[1] 熊红[1] 梁爱斌[1] 

机构地区：[1]同济大学附属同济医院血液科,上海200065 [2]同济大学附属同济医院检验科,上海200065

出　　处：《白血病．淋巴瘤》2009年第2期75-78,共4页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金（30572161）

摘　　要：目的探讨以血管内皮生长因子（VEGF）为靶点联合贝伐单抗（Bevacizumab，商品名：阿瓦斯丁，Avastin）和化疗药物诱导多种白血病细胞株凋亡的可行性，研究体外应用VEGF、贝伐单抗和化疗药物Ara-C对白血病细胞株增生、凋亡以及细胞周期的影响。方法应用不同浓度药物作用于体外培养的白血病细胞，CCK-8法检测细胞增生抑制率，流式细胞术（FCM）检测VEGF和贝伐单抗以及联合应用化疗药物后细胞周期和细胞凋亡的变化。结果VEGF可刺激多种细胞株增生，以U937细胞增生最明显，呈明显的量效关系；FCM检测细胞周期显示VEGF作用组S期细胞较对照组明显增多，而贝伐单抗作用组S期细胞减少；FCM检测显示经VEGF作用组细胞凋亡率较对照组细胞减少，而贝伐单抗作用组细胞凋亡率较对照组增加，但二者与对照组相比差异无统计学意义（P〉0．05），联合应用贝伐单抗和Ara-C 48h后，细胞凋亡率较单用Ara-C组明显升高（P〈0．05），联合VEGF、Ara-C组作用48h后，细胞凋亡率较Ara-C组降低（P〈0．05），同时联合应用VEGF、贝伐单抗和Ara-C组细胞凋亡率与Ara-C组差异无统计学意义（P〉0．05）。结论VEGF可明显刺激部分白血病细胞增长，抵抗化疗药物诱导的凋亡作用，贝伐单抗可通过中和VEGF而在一定程度上抑制细胞的增生，提高白血病细胞对化疗药物的敏感性。Objective To investigate the potential application of targeting at vascular endothelial growh factor （VEGF） induced apoptosis in leukemic cell lines by combined use of Bevacizumab and chemotherapeutic drug. Methods Leukemic cells were treated with several drugs at different concentrations in culture. The effect of VEGF, Bevacizumab and co-treated with Ara-C on leukemic cells proliferation were evaluated by CCK-8 and apoptosis and cell cycle were detected by flow cytometry （FCM）. Results VEGF could enhance the proliferation of leukemic cells and caused a dose-dependent manner on U937 cell. It also increased the percentage of cells in S phase, tested by, and Bevacizumab group was decreased. Apoptotic rate of cells treated with Bevacizumab or co-treated with Bevacizumab and Ara-C for 48 h were significantly higher when compared with control or Ara-C group, respectively （P 〈0.05）, but the apoptotic rate of VEGF group or VEGF and Ara-C group was lower （P 〉0.05）. There was no significant difference in apoptotic rate between control and combined use of VEGF, Bevacizumab and Ara-C group（P 〉0.05）. Conclusion VEGF could enhance the proliferation of some leukemic cells, and may contribute to leukemic cells survival and a resultant resistance to chemotherapy-triggered cell death. The study also showed that leukemic cells growth was significantly inhibited by Bevacizumab through directly against VEGF, and the sensitivity of leukemic ceils for chemotherapeutic drug was increased.

关 键 词：血管内皮生长因子 白血病 细胞株 细胞增生 贝伐单抗 

分 类 号：R733[医药卫生—肿瘤]