血管内皮生长因子-阿柔比星脂质体靶向杀伤恶性黑素瘤细胞的实验观察  

Targeted killing of malignant melanoma cells by aclarubicin liposome conjugated with vascular endothelial growth factor

作　　者：陈宏翔[1] 童强[2] 钱悦[1] 吴艳[1] 冯爱平[1] 吴志洪[1] 严小枫[1] 涂亚庭[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院皮肤性病科,武汉430022 [2]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022

出　　处：《中华皮肤科杂志》2008年第7期429-432,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金（30600535）

摘　　要：目的应用包裹阿柔比星的血管内皮生长因子（VEGF）的长循环脂质体（阿柔比星-VEGF-SSL）于体外靶向杀伤恶性黑素瘤细胞。方法通过体外结合试验，验证阿柔比星-VEGF—SSL对恶性黑素瘤A375细胞的特异结合能力。通过体外细胞毒试验（MTT），检测阿柔比星-VEGF—SSL对A375细胞增殖活性的影响。结果阿柔比星-VEGF—SSL可与A375细胞特异结合，结合率可达非特异性脂质体的2．15倍。阿柔比星-VEGF-SSL可特异抑制A375细胞的增殖活性。48h细胞毒试验阿柔比星-VEGF-SSL抑制A375细胞增殖活性的作用与游离阿柔比星相似（P〉0．05），优于无VEGF的阿柔比星脂质体（阿柔比星-SSL）（P〈0．05），而对非靶细胞（黑素细胞）增殖活性的抑制作用弱于两者。0．5h预处理试验表明：缩短药物与细胞接触时间后，阿柔比星-VEGF—SSL仍保持较强抑制A375细胞增殖活性的作用。结论阿柔比星-VEGF—SSL可特异性识别恶性黑素瘤A375细胞，并作为良好载体将阿柔比星带入瘤细胞，显著抑制A375细胞的增殖活性，实现其靶向杀伤作用。Objective To evaluate the targeted killing of malignant melanoma cells by aclarubicin liposomes conjugated with vascular endothelial growth factor （ADM-VEGF-SSL） in vitro. Methods To detect the binding ability of liposomes to malignant melanoma （MM） cells, the human malignant melanoma cell line A375 was cultured in the presence of ADM-VEGF-3H-SSL or ADM-3H-SSL for 2 days followed by the detection of radioactivity of these cells. Then, A375 cells were cultured with various concentrations （0.01, 0.1, 1, 10, 100 mol/L） of ADM-VEGF-SSL, ADM-SSL or free ADM for 48 hours in the 48-hour cytotoxity test, or for 0.5 hour followed by another 48-hour culture in drug-free medium in the 0.5-hour cytotoxity test. After that, MTT assay was used to detect the survival rate of these cells. Results ADM-VEGF-SSL could specifically bind to and kill A375 cells. The binding rate of ADM-VEGF-SSL was 2.15 folds as high as that of ADM-SSL. The survival rate of A375 cells after being treated with ADM-VEGF-SSL for 48 hour was similar to that with free ADM （P 〉 0.05）, but lower than that with ADM-SSL （P 〈 0.05 ）, while the survival rate of melanocytes treated with ADM-VEGF-SSL was higher than that with free ADM or ADM-SSL （both P 〈 0.05）. As shown by the 0.5-hour cytotoxity test, shortening the treatment course did not attenuate the effect of ADM-VEGF-SSL on A375 cells. Conclusions ADM-VEGF-SSL can specifically recognize A375 cells, efficiently deliver adriamycin into tumor cells, markedly inhibit the proliferation of A375 cells, and eventually, a targeted kill of these cells is realized.

关 键 词：黑色素瘤 受体 血管内皮生长因子 阿柔比星 脂质体 

分 类 号：R739.5[医药卫生—肿瘤] R735.2[医药卫生—临床医学]