Silencing of C-Myc to increase the sensitivity of acute lymphoblastic leukemia cells to cyclophosphamide

Abstract

Resistance to chemotherapy is a phenomenon that is seen in many cancers, including hematopoietic malignancies, and is one of the biggest problems in the treatment of these diseases. Resistance to chemotherapy in acute lymphoblastic leukemia (ALL) is no exception to this rule and has made treatment of this malignancy difficult. C-Myc factor has been shown to play a very important role in resistance to chemotherapy and leukemia cell growth. Therefore, in this study, it was decided to increase the susceptibility to cyclophosphamide-induced apoptosis in leukemic cells by inhibiting the expression of c-MYc factor. For this purpose, we used nanoparticles for simultaneous transfer of c-Myc siRNA and cyclophosphamide to leukemic cells. Materials and Methods: This study was performed on peripheral blood mononuclear cells obtained from 10 ALL patients and 10 normal individuals as well as Jurkat and NALM6 cell lines. Transfer of c-Myc siRNA and cyclophosphamide to cells was performed using superparamagnetic iron oxide nanoparticles (SPION) coated with trimethyl chitosan and hyaluronate. The effect of combination therapy on cell survival and apoptosis was assessed using MTT and flow cytometry. The expression of target genes was also assessed using real-time PCR. Results: Based on the results of this study, it was found that nanocarriers have good physicochemical properties that deliver siRNA and cyclophosphamide to target cells. Proper delivery of siRNA and drug reduced survival and induced apoptosis in cancer cells by regulating the expression of genes involved in apoptosis.