Blockade of mTOR in acute lymphoblastic leukemia cells to increase the cytotoxic effects of cyclophosphamide

Abstract

The existing treatments in a large number of patients with acute lymphocytic leukemia (ALL) have not accepted the results and limitations such as high cost for the patient or the treatment system, very severe side effects and inefficiency in the treatment of more advanced types. They have ALL. The ineffectiveness of these treatments led researchers to seek more effective and efficient treatments. On the other hand, several studies have shown the effectiveness of new combination therapies in combination with chemotherapy drugs such as cyclofsamide. Thus, this study, by showing the path of the proposed mechanism of action, focuses on presenting new therapies as a single target or by showing the consequences of combination therapies, on proposing goals with cooperative effects in combination. Materials and Methods: This study was performed on peripheral blood samples of 10 patients with ALL confirmed and 10 normal individuals as controls. Also, more information about some of the characteristics of patients such as recurrent genetic abnormalities, treatment approaches before relapse and remission related to patients and remission relapse, patients' gender, etc. were collected for additional evaluations. Peripheral blood samples were also collected from healthy donors in parallel and as a control group. In this study, cyclophosphamide, siRNA, and carrier nanoparticles were used as single agent and combination. Results: The results of this study showed that the nanoparticles produced with suitable physicochemical properties were able to transfect cancer cells well and suppress the expression of mTOR. In addition, inhibition of mTOR expression significantly increased the susceptibility of cancer cells to cyclophosphamide. Increased apoptosis in these cells was associated with increased Bax expression and decreased Bcl-2 expression.