乳糖化-去甲斑蝥素抗肿瘤药效学及急性毒性试验研究  

Study on Anti-tumor Pharmacodynamics and Acute Toxicity of Lac-NCTD

作　　者：管敏[1,2] 周奕[1] 贝永燕[2] 许静玉[2] 张学农[2] 

机构地区：[1]苏州大学药学院药剂学教研,江苏苏州215123 [2]苏州大学药学院06级药学本科实习生,江苏苏州215123

出　　处：《抗感染药学》2010年第3期171-175,共5页Anti-infection Pharmacy

基　　金：国家科技支撑计划课题资助(编号:2006BAI09B00);国家科技部科技型中小企业技术创新基金(立项代码:07C26223201333);江苏省"六大人才高峰"资助项目;国家大学生创新性实现课题(编号:57315924)

摘　　要：目的:观察乳糖化-去甲斑蝥素(Lac-NCTD)及其纳米粒(Lac-NCTD-NPs)的体内外抗肿瘤的作用,并进行急性毒性考察。方法:采用MTT法考察Lac-NCTD及Lac-NCTD-NPs对肿瘤细胞株HepG2、SMMC-7721和SGC-7901的细胞毒作用和半乳糖化小牛血清(Gal-FBS)的竞争性抑制作用,并建立H22肝癌细胞小鼠荷瘤模型考察药物在体内抗肿瘤活性;通过急性毒性实验计算Lac-NCTD腹腔给药的最大耐受量(MTD)。结果:HepG2、SMMC-7721细胞培养48h的体外细胞毒结果显示:Lac-NCTD-NPs的最强,其次是Lac-NCTD,且均能显著被Gal-FBS抑制;对SGC-7901,Lac-NCTD-NPs和Lac-NCTD的细胞毒作用并不比去甲斑蝥素(NCTD)强,且不受Gal-FBS的影响;体内抗肿瘤实验表明Lac-NCTD能有效地抑制H22肿瘤的生长。Lac-NCTD单次给药时最大耐受量MTD>20g/kg,多次给药时MTD>30g/kg,毒性远小于NCTD。结论:Lac-NCTD是毒性较小的安全的新型抗肿瘤药物。Objective：To analyze the primary pharmacodynamics of Lac-norcantharidin（Lac-NCTD）and Lac-norcantharidin nanoparticles（Lac-NCTD-NPs）,and to investigate the acute toxicity of the former.Methods：MTT colorimetric method was used to study the cytotoxic effects of Lac-NCTD and Lac-NCTD-NPs on HepG2,SMMC-7721 and SGC-7901 and the inhibition effects of Gal-FBS.The H22 hepatoblastoma cell line mice was established to evaluate the in vivo anti-tumor activity of Lac-NCTD and Lac-NCTD-NPs.The maximum tolerated dose（MTD）for Lac-NCTD was calculated by acute-toxicity test by intraperitoneal injection.Results：The ASGP-R on the surface of HepG2 and SMMC-7721 can recognizes the galactose residue of Lac-NCTD,therefore,the cytotoxic effects of Lac-NCTD and Lac-NCTD-NPs on these two cell lines were stronger than NCTD and they were inhibited significantly by Gal-FBS.Lac-NCTD showed powerful anti-tumor activity in vivo on the hepatoblastoma cell line.Acute toxicity test demonstrates that the compound Lac-NCTD is safe.Conclusion：The compound Lac-NCTD is safe and shows powerful anti-tumor activity.

关 键 词：乳糖化-去甲斑蝥素 急性毒性 抗肿瘤 药效学 

分 类 号：R965[医药卫生—药理学]