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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 investigate the antitumor effects of Lac-NCTD and Lac-NCTD-NPs in vivo and in vitro, and to investigate acute toxicity. METHODS: The cytotoxicity of Lac-NCTD and Lac-NCTD-NPs on tumor cell lines HepG2, SMMC-7721 and SGC-7901 and competitive inhibition of galactosed calf serum (Gal-FBS) were investigated by MTT assay. A mouse tumor model of H22 hepatocarcinoma cells was established to investigate the anti-tumor activity of the drug in vivo; the maximum tolerated dose (MTD) of Lac-NCTD administered intraperitoneally was calculated by acute toxicity experiments. RESULTS: In vitro cytotoxicity of HepG2 and SMMC-7721 cells cultured for 48 h showed that Lac-NCTD-NPs were the strongest, followed by Lac-NCTD, and both were significantly inhibited by Gal-FBS; SGC-7901, Lac-NCTD The cytotoxicity of -NPs and Lac-NCTD was not stronger than that of norcantharidin (NCTD) and was not affected by Gal-FBS. In vivo anti-tumor experiments showed that Lac-NCTD can effectively inhibit the growth of H22 tumors. The maximum tolerated dose of Lac-NCTD was greater than 20 g/kg in single doses, and the MTD was more than 30 g/kg in multiple doses. The toxicity was much less than that of NCTD. Conclusion: Lac-NCTD is a safe, new and novel anti-tumor drug.