Study of the mechanism of action of cytostatic drug regimens with the addition of lysine acridone acetate in metastatic colorectal cancer

Abstract

Background. One of the most common malignant tumors is colorectal cancer. Colorectal cancer is characterized by frequent metastasis to the liver, lungs, peritoneum and distant lymph nodes, and therefore its treatment is complicated. Therefore, it is urgent to search for new drugs and treatment methods based on the molecular mechanisms underlying metastatic colorectal cancer.Aim. To study the mechanism of action of cytostatic drug regimens with the addition of lysine acridone acetate to increase the effectiveness of anti-oncogenic chemotherapy in metastatic colorectal cancer.Materials and methods. We used mice of Nude line at the age of 4 weeks with inoculated tumor cells of SW837 line, which were administered chemotherapy drugs (FOLFOXIRI и FOLFOX6). On biopsy samples of liver metastases, the apoptosis level (TUNEL) and the expression of proteins CD95, p53, BCL2, histone H3, Ki-67 (immunohistochemistry) were assessed.Results. An activating effect of the studied therapeutic regimens was revealed, which was more active with the addition of lysine acridone acetate, on the development of p53-dependent apoptosis and the expression of H3K27me3 (a marker of treatment effectiveness and tumor progression) in colorectal cancer metastases in the liver of experimental mice. At the same time, the level of cancer cell proliferation (Ki-67 expression) decreased.Conclusion. Increased apoptosis in mouse liver metastases, as well as a decrease in cancer cell proliferation when using these drug regimens should be regarded as a positive therapeutic effect. A p53-dependent mechanism of apoptosis activation under the influence of appropriate treatment regimens has been revealed. Lysine acridone acetate may be preferable for clinical study.