Evaluation of the effect of nano-encapsulated lactoferrin on the expression of Bak and Bax genes in gastric cancer cell line AGS and study of the molecular docking of lactoferrin with these proteins

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.