胶质细胞源性神经营养因子-壳聚糖纳米脂质载体通过抑制NF-κB活性抑制肠癌

Liangrun Zhu, Qi-sheng Jiang, Jun Fang, Gang Bian
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引用次数: 0

摘要

背景:胶质细胞源性神经营养因子(GDNF)是一种有效的神经营养因子,可影响癌症细胞的转移和侵袭。GDNF的分子机制尚不清楚。在此,我们研究了壳聚糖(CS)纳米脂质载体包埋GDNF在结直肠癌中的作用机制。方法:采用电镜技术检测GDNF壳聚糖(CS)包被纳米脂质载体的特性与细胞凋亡的关系,采用MTT法和细胞凋亡法检测GDNF-壳聚糖纳米脂质载体表达对肠道癌症细胞增殖能力的影响,免疫荧光法检测GDNF壳聚糖纳米脂质载体表达对NF-KB信号的影响。结果经蛋白质印迹法验证。在体内使用小鼠模型。结果:壳聚糖-壳聚糖纳米脂质载体显示出正ζ值,表明CS包被GDNF的工艺是成功的。用紫外分光光度计和MTT法测定了不同浓度下纳米复合材料的OD值。我们的数据显示,实验组表现出依赖于耐受生长的浓度和剂量关系,表明GDNF壳聚糖纳米脂质载体对结直肠癌癌症细胞系具有更好的抗肿瘤活性。与大多数GDNF壳聚糖纳米脂质载体组相比,大肠癌组织中NF-κB免疫荧光检测信号的表达受到抑制,NF-κB表达下调。体内结果显示,用GDNF-壳聚糖纳米粒子脂质载体处理后,测量的肿瘤体积减少,用GDNF-壳聚糖纳米粒子脂载体处理的小鼠的存活时间更长。结论:GDNF壳聚糖纳米脂质载体在体内可抑制NF-κB信号的表达,减少肿瘤的增殖,从而减缓肠道癌症细胞的发生和发展。
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Glial Cell Line-Derived Neurotrophic Factor Chitosan Nanolipid Carrier Inhibits Intestinal Carcinoma via Restraining NF-κB Activity
Background: Glial cell line derived neurotrophic factor (GDNF) is a potent neurotrophic factor, which has been shown to affect the metastasis and invasion of cancer cells. The molecular mechanism of GDNF is still unclear. Here, we investigate the mechanism of GDNF embedded in chitosan (CS) nano lipid carrier in colorectal cancer. Methods: Electron microscopy was used to detect the relationship between the characteristics of GDNF chitosan (CS) coated nano lipid carrier, MTT and apoptosis tests were used to detect the effect of GDNF chitosan nano lipid carrier expression on the proliferation ability of intestinal cancer cells, and immunofluorescence was used to detect the effect of GDNF chitosan nano lipid carrier expression on NF-KB signal. The results were verified by western-blot. In vivo using a mouse model. Results: GDNF chitosan nano lipid carrier showed positive zeta value, indicating that the process of CS coating GDNF was successful. OD values of nanocomposites at different concentrations were measured by UV spectrophotometer with MTT. Our data showed that the experimental group showed a relationship between concentration and dose dependent on tolerance growth, indicating that GDNF chitosan nano lipid carrier had better anti-tumor activity in colorectal cancer cell lines. Compared with most GDNF chitosan nano lipid carrier groups, the expression of NF-κB immunofluorescence detection signal was inhibited, and the expression of NF-κB was down-regulated in colorectal cancer. In vivo results showed that the measured tumor volume decreased after treatment with GDNF chitosan nanoparticle lipid carrier, and the survival of mice treated with GDNF chitosan nanoparticle lipid carrier was longer. Conclusion: GDNF chitosan nano lipid carrier can inhibit the expression of NF-κB signal and reduce the proliferation of tumor In vivo, thus slowing down the occurrence and development of intestinal cancer cells.
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