Anticancer signal transduction pathways of selenium nanoparticles in mouse colorectal cancer model

Despite significant advances in the treatment of colon cancer, this disease is extremely common, often requiring serious surgery followed by long-term drug treatment. Colon and rectal cancer remain dangerous forms of cancer due to the high degree of metastasis. The development and study of the effectiveness of anticancer drugs based on nanoparticles is an urgent task of modern biomedicine. Of particular interest are attempts to move research from the in vitro level to the in vivo level of preclinical studies. In the presented study, mice were subcutaneously implanted with MC-38 cell line, a tumor was grown, and selenium nanoparticles (SeNPs) with a diameter of 100 nm obtained using the laser ablation method were administered intraperitoneally. Using morphometric measurements, it was found that injections of 1 μg/g or 10 μg/g SeNPs inhibited weight loss of mice during cancer development, reduced tumor size by 2-2.5 times, and suppressed metastasis by 1.5-3 times. Analysis of selenium levels in mouse blood, liver and tumor samples by atomic absorption spectrometry after the end of SeNPs treatment showed that the nanoparticles increased selenium levels in the blood and liver of mice without a significant dose-dependence, whereas in tumors a dose-dependent increase in selenium concentration was detected from the concentration of nanoparticles, with 10 μg/g SeNPs causing a more pronounced increase in selenium concentration. Using PCR and Western blot analysis, it was possible to establish that SeNPs injections led to an increase in the expression of genes encoding anti-inflammatory and anti-hypoxic proteins, but reduced the expression of antioxidant selenium-containing proteins and proteins responsible for the proliferation of cancer cells. Both concentrations of SeNPs led to similar effects, but increasing the concentration of nanoselenium to 10 μg/g affected the expression of a larger number of genes and the effects on expression were more "bright". Thus, the complex of presented experiments showed that injections of selenium nanoparticles in concentrations of 1 μg/g or 10 μg/g are capable to transport by the bloodstream and accumulating in the highest concentration in colon adenocarcinoma, compared with liver, which indicates the targeting of SeNPs in relation to tumors even without functionalization by specific molecules. As a result, there was a change in the expression patterns of genes and a number of proteins, and as a result, there was a decrease in tumor volume, normalization of mouse weight and maintenance of positive dynamics throughout the entire observation period.