羟基喜树碱联合热疗抑制血管生成作用的实验研究.docVIP

羟基喜树碱联合热疗抑制血管生成作用的实验研究 钱晓萍，刘宝瑞，胡静，胡文静，杨阳，禹立霞 南京大学医学院附属鼓楼医院肿瘤中心，江苏 南京，210008 摘要： 目的 探讨羟基喜树碱联合应用热疗对体内外血管生成的抑制作用。方法 采用MTT法观察羟基喜树碱联合热疗对人微血管内皮细胞（HMVEC）、人肝癌细胞HepGⅡ增殖的影响。利用三维血管模型观察羟基喜树碱联合热疗对HMVEC迁移的影响。利用鸡胚绒毛尿囊膜（CAM）模型，观察羟基喜树碱对鸡胚绒毛尿囊膜血管生成的影响。结果 羟基喜树碱在5-80ng/ml浓度范围内，具有抑制血管内皮细胞增殖和迁移作用（内皮细胞存活率在98.4%-37.6%），均与浓度呈负相关（相关系数分别为-0.906、-0.469，P值分别为0.00003、0.0051）；具有抑制鸡胚绒毛尿囊膜血管生成的作用；而在该浓度范围内，对人肝癌细胞无细胞毒作用（细胞存活率在100%-90%之间）。20ng/ml的羟基喜树碱与热疗联合应用在体外具有抗血管生成的协同效应；40ng/ml的羟基喜树碱与热疗联合应用在体外具有抗血管生成的次加效应。结论 小剂量羟基喜树碱（5-80ng/ml）联合热疗在体内外均具有抑制血管增殖和迁移协同作用。 关键词： 羟基喜树碱；内皮细胞；抗血管生成；热疗 The Experimental Research on the Inhibiting Angiogenesis Effect of Hydroxycamptothecin With Thermotherapy QIAN Xiao-ping, LIU Bao-rui, HU Jing （Cancer Center of Nanjing University Medical College Affiliated Drum Tower Hospital, Nanjing, Jiangsu Province,210008） ABSTRACT：Objective To study the effects of Hydroxycamptothecin with thermotherapy on anti-angiogenesis in vitro and in vivo. Methods We adopt human microvascular endothelial cell (HMVEC) culture and chick embryo choriallantoic membrane (CAM) model and use MTT and number-calculating methods to observe hydroxycamptothecine on HMVEC’s proliferation , sprouts and CAM blood vessels’ formation. Results The survival rate of endothelial cells is among 98.4%-37.6% within the dose of 5-80ng/ml and is negative correlated with the concentration (correlation coefficient is –0.906,-0.469, P0.00003、0.0051). Hydroxycamptothecine can significantly suppress the endothelial cells’ proliferation and the sprouts. Hydroxycamptothecine can significantly suppress CAM vessels. The survival rate of HepG II cells is among 100%-90% within the dose of 5-80ng/ml. There is no cytotoxicity. There is a synergedtic effection in anti-angiogenetic when combined use hydroxycamptothecin (20ng /ml) with thermotherapy in vitro while addition effection whin hydroxycamptothecin (40ng/ml) with thermotherapy in vitro. Conclution This experiment shows that small dose hydroxycamptothecine (5-80ng/ml) with th