关键词: Apoptosis Bak Bax Gastric cancer Nano-encapsulated lactoferrin

Mesh : Humans Apoptosis bcl-2 Homologous Antagonist-Killer Protein / genetics metabolism bcl-2-Associated X Protein / genetics metabolism Cell Line Molecular Docking Simulation Stomach Neoplasms / drug therapy genetics metabolism Lactoferrin / pharmacology

来  源:   DOI:10.1016/j.gene.2023.147355

Abstract:
lactoferrin (Lf) is a glycoprotein with various biological activities, including antibacterial, antiviral, anti-cancer, etc. In the present study, the effect of different concentrations of nano-encapsulated lactoferrin (NE-Lf) on the expression of Bax and Bak genes was evaluated in stomach cancer cell line AGS using real-time PCR technique and cytotoxicity of NE-Lf on the growth cells as well as the molecular mechanism of these two genes and their proteins in the apoptosis pathway and the relationship between lactoferrin and these proteins were investigated by bioinformatics studies. In the viability test, the results showed that the growth inhibition effect of nano-lactoferrin was greater than lactoferrin in both concentrations, and chitosan had no inhibitory effect on the cells. In concentrations of 250 and 500 µg of NE-Lf Bax gene expression increased by 2.3 and 5 times, respectively, and Bak gene expression increased by 1.94 and 1.74 times, respectively. Statistical analysis showed that there is a significant difference in the relative amount of gene expression between the treatments in both genes (P < 0.05). The binding mode of lactoferrin with Bax and Bak proteins was obtained using docking. According to docking results, the N-lobe region of lactoferrin interacts with the Bax protein, as well as the Bak protein. The results show that lactoferrin, in addition to acting on the gene, interacts with Bax and Bak proteins. Since two proteins are components of apoptosis, lactoferrin can induce apoptosis in this way.
摘要:
乳铁蛋白(Lf)是一种具有多种生物活性的糖蛋白,包括抗菌,抗病毒,抗癌,等。在本研究中,使用实时PCR技术评估了不同浓度的纳米包裹的乳铁蛋白(NE-Lf)对胃癌细胞系AGS中Bax和Bak基因表达的影响,并通过生物信息学研究了NE-Lf对生长细胞的细胞毒性以及这两个基因及其蛋白在凋亡途径中的分子机制以及乳铁蛋白与这些蛋白之间的关系。在生存能力测试中,结果表明,在两种浓度下,纳米乳铁蛋白的生长抑制作用均大于乳铁蛋白,壳聚糖对细胞无抑制作用。在浓度为250和500μg的NE-Lf中,Bax基因表达增加了2.3和5倍,分别,Bak基因表达分别增加1.94和1.74倍,分别。统计学分析表明,两种基因处理间的基因表达量存在显著差异(P<0.05)。使用对接获得乳铁蛋白与Bax和Bak蛋白的结合模式。根据对接结果,乳铁蛋白的N叶区域与Bax蛋白相互作用,以及Bak蛋白。结果表明,乳铁蛋白,除了作用于基因,与Bax和Bak蛋白相互作用。由于两种蛋白质是细胞凋亡的组成部分,乳铁蛋白可以通过这种方式诱导细胞凋亡。
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