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

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.