Combination Therapy with miR-34a and Doxorubicin Synergistically Induced Apoptosis in T-Cell Acute Lymphoblastic Leukemia Cell Line [post]

Shiva Najjary, Reza Mohammadzadeh, Behzad Mansoori, Fatemeh Vahidian, Ali Mohammadi, Mohammad Amin Doustvandi, Vahid Khaze, Khalil Hajiasgharzadeh, Behzad Baradaran
2021 unpublished
Reduced expression of tumor suppressor miRNAs leads to cancer cell development, so restoring the expression of these miRNAs can be an appropriate treatment option for cancer. Due to the heterogeneity of cancer cells, single-drug therapy often results in drug resistance. Therefore, the combination of chemotherapy with miRNA can be a powerful strategy for cancer treatment. In the current investigation, we researched the synergic effect of miR-34a in combination with doxorubicin (DOX) on cell
more » ... of acute T-cell lymphoblastic leukemia (T-ALL) Jurkat cell line, as well as the expression of some genes including Caspase-3, Bcl-2, and p53 which are involved in apoptosis. Our outcomes showed that the combination of miR-34a and doxorubicin remarkably reduced the expression of the Bcl-2 gene, the target gene of miR-34a. According to the results of the MTT assay in cells treated with miR-34a and doxorubicin, the survival rate was significantly decreased compared to the untreated cells. Results of the flow cytometry assay and DAPI staining demonstrated an increased apoptosis rate of Jurkat cells in combination therapy. Moreover, cell cycle arrest was observed at the G2/M phase in cells that were treated with miR-34a/doxorubicin. Most importantly, we showed that the transfection of the Jurkat cells with miR-34a increased the sensitivity of these cells to doxorubicin. Furthermore, the combination of miR-34a and doxorubicin drug effectively increased apoptosis of treated cells. Therefore, this method can be used as an impressive treatment for T-ALL.
doi:10.21203/rs.3.rs-837119/v1 fatcat:x5k5q4ie7nf2jnqhtgefow6cfi