青蒿素衍生物对宫颈癌细胞血管形成相关分子表达和人脐静脉内皮细胞血管形成能力的影响  

Effect of artemisinin derivatives on the expression of angiogenesis-related molecules in cervical cancer cell and the angiogenic ability of human umbilical vascular endothelial cell

作　　者：吕江涛[1] 杨华[1] 郎景和[1] 谭先杰[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院妇产科,协和转化医学中心,北京100730

出　　处：《现代妇产科进展》2013年第11期877-880,共4页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:30973177)

摘　　要：目的:探讨两种青蒿素衍生物(双氢青蒿素和青蒿琥酯)对宫颈癌细胞血管形成相关分子表达水平和人脐静脉内皮细胞(HUVEC)血管形成能力的影响;方法:培养HeLa和Caski细胞,分别给予双氢青蒿素和青蒿琥酯处理。采用ELISA法分别于不同时间点测定上清液中血管内皮细胞生长因子(VEGF)和血小板反应素-1(TSP-1)浓度;72h后留取经双氢青蒿素处理的细胞,提取其总RNA进行RT-PCR,测定VEGF和TSP-1的mRNA水平。原代培养HUVEC,分别给予双氢青蒿素和青蒿琥酯处理,72h后MTT法检测HUVEC的增殖情况;将HUVEC与双氢青蒿素混匀后接种于管样结构形成模型,12h后观察管样结构形成情况。结果:双氢青蒿素和青蒿琥酯对VEGF和TSP-1浓度无影响;双氢青蒿素对宫颈癌细胞VEGF mRNA的表达无影响,但可促进TSP-1 mRNA的表达。两种青蒿素衍生物对HUVEC体外增殖能力均有抑制作用,且存在浓度和时间依赖性;双氢青蒿素对HUVEC管样结构形成能力有抑制作用。结论:青蒿素衍生物可能通过对血管内皮细胞的直接作用而发挥抗肿瘤血管形成效应。Objective ： To investigate the effect of two artemisinin derivatives （ dihydroartemisinin and artesunate） on the expression of vascular endothelial growth factor （VEGF） and thrombospondin-1 （TSP-1） in cervical cancer cell and on the the angiogenic ability of hu- man umbilical vascular endothelial cell （HUVEC）. Methods： HeLa and Caski cell were cultured with different concentrations of dihydroartemisinin and artesunate respectively. The concentrations of VECF and TSP-1 in supernatant at different points in time were measured by ELISA. 72 hours later,total RNA in the cells exposed to dihydroartemisinin were extracted,and then the level of VEGF mRNA and TSP-1 mRNA were determined by RT-PCR. HUVEC were cultured with different concentrations of dihydroartemisinin and artesunate respectively for 72 hours. The effect of the drugs on the proliferation of HUVEC was observed by MTT assay. The capillary-like structures formation models was applied to observe the effect of dihydroartemisinin on the angiogenic ability of HUVEC in vitro. Result：Dihydroartemisinin and artesunate had no effects on the concentrations of VEGF and TSP-1. TSP-1 mRNA could be up-regulated by dihydroartemisinin,while VEGF mRNA could not. The proliferation of HUVEC could be suppressed by both two artemisinin derivatives in a concentration-dependent and time-dependent way. Dihydroartemisinin also could suppress the tube-like structure formation of HUVEC in vitro. Conclusions：The mechanisms by which the artemisinin derivatives might exert the suppressive effects on tumor angiogenesis is through direct inhibition on vascular endothelial cell.

关 键 词：青蒿素 宫颈癌 人脐静脉血管内皮细胞 血管形成抑制剂 

分 类 号：R737.3[医药卫生—肿瘤]