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论著:半乳糖基壳聚糖5氟尿嘧啶纳米粒的制备及其抑制小鼠结肠癌的实验研究
Preparation of 5-Fluorouracil Nanoparticles of Galactosylated Chitosan and Its Inhibition of the Colon Cancer in Mice
何秉 程明荣 万涛 陈厚祥 程志俭 叶桃 徐宏智 侯益明
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作者单位:复旦大学附属上海市第五人民医院普外科
中文关键字:5氟尿嘧啶;壳聚糖;半乳糖;结肠癌肝转移
英文关键字:5-Fluorouracil; Chitosan; Galactose; Colon cancer
中文摘要:目的:半乳糖基壳聚糖纳米材料与5-氟尿嘧啶(5-FU)合成5-FU纳米粒,并观察其在体内抑制小鼠结肠癌的疗效。方法:将体外培养的C26细胞接种小鼠肝左叶,成瘤后,分别用0.9%氯化钠液、空纳米粒、5-FU和5-FU纳米粒行尾静脉注射,观察5-FU纳米粒的抗肿瘤效果。用酶联免疫吸附试验法检测血清γ干扰素(IFN-γ)和白细胞介素-2(IL-2)含量,用四甲基偶氮唑盐(MTT)比色法测定小鼠脾自然杀伤细胞(NK细胞)和细胞毒性T细胞(CTL细胞)活性。结果:与0.9%氯化钠液组及纳米粒组相比,5-FU组和5-FU纳米粒组的瘤质量显著降低(P<0.01),尤其5-FU纳米粒组降低更显著(P<0.01)。与其他各组比较,5-FU组小鼠,外周血IFN-γ和IL-2含量均显著降低(P<0.01),5-FU纳米粒组与0.9%氯化钠液组比较差异无统计学意义(P>0.05)。5-FU组的脾NK细胞和CTL细胞杀伤活性较其他各组显著降低(P<0.01), 5-FU纳米粒组与0.9%氯化钠液组比较未见降低(P>0.05),纳米粒组NK和CTL杀伤活性0.9%氯化钠液组增高(P<0.05)。结论:5-FU纳米粒治疗结肠癌模型,具有明显抗肿瘤效应,纳米粒材料具有提高机体免疫功能,减低5-FU对机体免疫的抑制作用。
英文摘要:Objective: The 5-fluorouracil (5-Fu) nanoparticles of galactosylated chitosan was synthesized and the efficacy were observed in colon cancer model in vivo with 5-fluorouracil nanoparticles of galactosylated chitosan. Methods: C26 cells were cultured left lobe of the liver in mice, after tumor formation, models were treated with normal saline in NS group, empty nanoparticles in NP group,5-Fu nanoparticles in 5-Fu NP group and 5-Fu in 5-Fu group, respectively, via tail vein injection. Tumor weight were measured in the end of this experiment. The serum interferon-gamma (IFN-γ) and interleukin-2 (IL-2) were detected by enzyme-linked immunospot-based assays (ELISA), and natural killer (NK) cells and cytotoxic T lymphocytes (CTL) activity of mouse spleen were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium(MTT) colorimetric assay. Results: Compared with NS group and NP group, the tumor weight in 5-Fu group and group was significantly lighter (P<0.01), the tumor weight decreased more obvious in 5-Fu NP group(P<0.01). The levels of IFN-γ and IL-2 of liver metastases of colon cancer model in mice decreased obviously in 5-Fu group than those in other groups(P<0.01), however, the decrease of IFN-γ and IL-2 in 5-Fu NP group was not obvious (P> 0.05), compared with the saline group, while the levels in NP group was significantly higher than those in NS group(P<0.01). The killing activity of NK and CTL in 5-Fu group was significantly lower than that in other groups (P<0.01), however, the killing activity of NK and CTL in NP group increased compared with NS group (P<0.05), and 5-Fu NP group was no lower compared with NS group (P> 0.05). Conclusions: The 5-Fu nanoparticles have significant anti-tumor effect in colon cancer model, nanoparticle materials can stimulate immune function of mice and reduced the side effects of 5-Fu in immune suppression.
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