人造靶点免疫导向阿霉素对荷肉瘤小鼠瘤质量及生存期的影响  

Anti-human IgG-dextran-adriamycin conjugate for immunotargeting of S180 sarcoma:effects on the tumor weight and survival time of the tumor-bearing mice

作　　者：张婧[1] 罗敏[1] 周媛[1] 张积仁[1] 

机构地区：[1]南方医科大学珠江医院肿瘤中心,广东广州510282

出　　处：《南方医科大学学报》2008年第4期646-648,共3页Journal of Southern Medical University

摘　　要：目的制备小鼠抗人IgG-葡聚糖-阿霉素免疫靶向偶联物,在肿瘤组织中接种人IgG非特异性靶点,探讨人造靶点免疫导向治疗肿瘤的可行性。方法制备小鼠抗人IgG-葡聚糖-阿霉素(阿霉素)偶联物,建立荷瘤小鼠模型。采用ELISA法测定小鼠抗人IgG-葡聚糖-阿霉素偶联物抗体活性;体外细胞毒性实验比较分析小鼠抗人IgG、游离阿霉素、小鼠抗人IgG-葡聚糖-阿霉素对S180细胞的毒性作用,比较阿霉素、小鼠抗人IgG-葡聚糖-阿霉素、小鼠抗人IgG-葡聚糖-阿霉素+人IgG的抑瘤作用及对荷瘤小鼠生存时间的影响。结果制备的偶联物中,小鼠抗人IgG、葡聚糖与阿霉素物质的量比为1∶2.5∶38;偶联物保留了小鼠抗人IgG抗体活性;体外细胞毒性实验表明偶联物对S180细胞有体外杀伤作用。小鼠抗人IgG-葡聚糖-阿霉素+肿瘤中接种人IgG组对小鼠移植性S180肉瘤的抑瘤率达17.72%,与其他组比较有显著性差异,但并未延长荷瘤小鼠的生存时间。结论通过在肿瘤组织中接种IgG非特异性靶点,用抗人IgG单克隆免疫靶向阿霉素治疗小鼠S180肉瘤较对照组具有靶向作用。Objective To prepare anti-human IgG-dextran-adriamycin conjugate for immunotargeting of S 180 sarcoma and assess its effects on the tumor weight and survival time of the tumor-bearing mice. Methods Anti-human IgG-dextranadriamycin was synthesized by conjugating dextran and adriamycin with anti-human IgG. The immunoactivity of anti-human IgG-dextran-adriamycin was measured by enzyme-linked immunosorbent assay （ELISA）, and the cytotoxicity of anti-human IgG, adriamycin, and the IgG-dextran-adriamycin conjugate against the tumor cells in vitro was evaluated using MTT assay. In mice bearing S 180 sarcoma, the agents were tested for their effects against tumor cell growth and the survival time of mice. Results The molar ratio of anti-mouse IgG, dextran, and adriamycin was 1：2,5：38 in the conjugate. The conjugates were shown to retain the immunoactivity of anti-human IgG, and possessed cytotoxicity to S 180 cells in vitro. Administration of the conjugate and intratumor injection of human IgG resulted in a tumor suppression rate of 17.72% in mice bearing S180 sarcoma, but did not prolong the survival time of the mice. Conclusion The anti-human IgG-dextran-adriamycin conjugate shows targeted antitumor effect against S180 sarcoma in mice.

关 键 词：阿霉素 靶向偶联物 小鼠肉瘤S180 抑瘤率 

分 类 号：R73-36[医药卫生—肿瘤]