Multiple drug resistance phenotype of human endothelial cells induced by vascular endothelial growth factor 165  

血管内皮生长因子165诱导人血管内皮细胞多药耐药表型(英文)

作　　者：张晓实[1] 朱孝峰[1] 高劲松 钱朝南[1] 邝珠玑[1] 刘宗潮[1] 曾益新[1] 

机构地区：[1]中山医科大学肿瘤防治中心 [2]达安基因研究中心,广州中国510060

出　　处：《Acta Pharmacologica Sinica》2001年第8期731-735,共5页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China (No 39900183);211 Projects in Sun Yat-sen University of Medical Sciences (No 98069)

摘　　要：AIM: To investigate the effect of vascular endothelial growth factor 165 (VEGF165) on sensitivity of endothelial cells to anticancer drugs. METHODS: Human dermal microvessel endothelial cells (HDMEC) were incubated with anticancer drugs in the presence of VEGF165. Survival of endothelial cells was assayed by MTT method. DNA fragments of apoptosis were detected by agarose electrophoresis. Potential mechanisms underlying the effect of VEGF165 on endothelial cells were investigated with RT-PCR and Western blot analysis. RESULTS: VEGF165 induced the multidrug resistance phenotype of HDMEC to a wide variety of anticancer drugs such as epirubicin, cisplatin, etoposide, mytomycin C, vin-cristine, CPT-11, and taxol in vitro. This protective effect was partly due to the up-regulation of lung drug resistance protein (LRP) and multidrug resistance-associated protein (MRP), as well as the down-regulation of Bax protein induced by VEGF165. CONCLUSION: VEGF165 induced multidrug resistance phenotype of endothelial cells, which implicated the anti-angiogenic effect of anticancer drugs might depend on microenviron-ment of tumors in vivo.目的:研究血管内皮生长因子165(VEGF_(165))对血管内皮细胞药物敏感性的影响。方法:人真皮微血管内皮细胞(HDMEC)与抗癌药物和VEGF_(165)混合培养,MTT法分析药敏变化,琼脂糖电泳检测细胞凋亡,RT-PCR、免疫印迹法分析HDMEC产生多药耐药表型的机制。结果:VEGF_(165)体外诱导HDMEC对多种抗癌药物耐药,如表柔比星、顺铂、足叶乙甙、丝裂霉素C、长春新碱、CPT-11、泰素等,其机制与VEGF_(165)诱导HDMEC上调表达多药耐药相关蛋白和肺耐药相关蛋以及下调表达Bax蛋白有关。结论:VEGF_(165)诱导血管内皮细胞的多药耐药表型,提示化疗时抗癌药物的抗血管生成活性可能取决于肿瘤微环境。

关 键 词：endothelial growth factors endotheli-um multiple drug resistance apoptosis CYTOTOXICITY drug therapy Western blotting polymerase chain reaction ELECTROPHORESIS 

分 类 号：R73-36[医药卫生—肿瘤]