Investigating the impact of NET1 silencing on apoptotic effects of Methotrexate in acute lymphoblastic leukemia

Abstract

Immunotherapy is one of the new and effective ways to treat cancers including leukemias. Acute lymphocytic leukemia (ALL) is a common blood malignancy. Despite its advances, no effective treatment has yet been found. Although chemotherapy is still the first choice for controlling the disease, the effectiveness of this method varies from patient to patient, and resistance is found in many patients. Therefore, finding ways that can increase the effectiveness of chemotherapy and increase the sensitivity of cells to chemotherapy is one of the research priorities of many researchers. In this study, it was decided to increase the sensitivity of leukemic cells to methotrexate by inhibiting the expression of net1, which plays an important role in resistance to treatment. Materials and Methods: This study was performed on peripheral blood mononuclear cells of 10 ALL patients and 10 normal individuals as well as Jurkat and NALM-6 cell lines. In order to induce methotrexate sensitivity in malignant cells, carboxymethyl dextran-coated trimethyl chitosan nanoparticles were used to deliver NET-1 siRNA and methotrexate to cells. After cell transfection, the effect of the combined text on cell survival and expression of target genes was evaluated. Results: The results of this study showed that the appropriate physicochemical properties of synthesized nanoparticles cause effective transfection of malignant cells. Cell transfection effectively reduced cell survival and induced apoptosis in cancer cells. Also, combination therapy significantly reduced the expression of factors involved in the growth and spread of malignant cells.