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Combination therapy with miR-34a and doxorubicin synergistically induced apoptosis in T-cell acute lymphoblastic leukemia cell line

Abstract

MicroRNAs are identified to take actively part in the development of different cancers. 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, miR-34a mimic, and negative control were purchased and transfected using jetPEI reagents. Then the synergic effects of miR-34a in combination with doxorubicin were investigated on cell death of acute T-cell lymphoblastic leukemia 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 this combination remarkably reduced the expression of the Bcl-2 gene, the target gene of miR-34a. According to the results of the MTT assay, 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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the research staff at the Immunology Research Center, Tabriz University of Medical Sciences for assistance in performing experiments.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors

Contributions

SN, and BB devised the main conceptual ideas and participated in the design of the work. BB provided biological materials and reagents. SN, BM, FV, AM, and MAD performed the experiments. SN, and KH wrote the initial draft of the manuscript. SN, BM, VK, and RM participated in the analysis of the work and reviewed and edited the manuscript. BB, and RM supervised the study.

Corresponding authors

Correspondence to Reza Mohammadzadeh or Behzad Baradaran.

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All experiments and procedures were conducted in compliance with the ethical principles of Tabriz University of Medical Science, Tabriz, Iran and approved by the regional ethical committee for medical research.

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Najjary, S., Mohammadzadeh, R., Mansoori, B. et al. Combination therapy with miR-34a and doxorubicin synergistically induced apoptosis in T-cell acute lymphoblastic leukemia cell line. Med Oncol 38, 142 (2021). https://doi.org/10.1007/s12032-021-01578-8

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Keywords

  • miR-34a
  • Doxorubicin
  • Apoptosis
  • T-cell acute lymphoblastic leukemia (T-ALL)