中华皮肤科杂志 ›› 2008, Vol. 41 ›› Issue (7): 429-432.

• 论著 •    下一篇

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

陈宏翔 童强 钱悦 等   

  1. 华中科技大学同济医学院附属协和医院 武汉市协和医院皮肤科 武汉协和医院皮肤科
  • 收稿日期:2007-07-03 修回日期:2007-12-21 发布日期:2008-07-15
  • 通讯作者: 陈宏翔 E-mail:hongxiangchen@hotmail.com;wslhss@163.com

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

  

  • Received:2007-07-03 Revised:2007-12-21 Published:2008-07-15

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。48 h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。0.5 h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。

Abstract: 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.