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siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468)

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Abstract

CD44, as a superficial cellular glycoprotein, is an essential factor in cell–cell and cell–matrix interaction. The CD44 expression level has been substantially up-regulated in breast cancer, and this upregulation facilitates tumor proliferation and angiogenesis. This study aims to evaluate the combination therapy of Jet Pei/CD44-specific-siRNA/doxorubicin in breast cancer MDA-MB468 cell line. The MTT assay, wound healing test, colony formation assay, DAPI staining, and flow cytometry were performed to investigate the tumoral cell viability, migration, clonogenesis, and apoptosis progression. The quantitative real-time PCR (qRT-PCR) was performed to demonstrate the CD44 expression level. Finally, the effect of CD44 silencing on the expression of VEGF, CXCR4, MMP9, and MiR-142-3p was measured. The combination of CD44-specific-siRNA with doxorubicin decreased tumoral metastasis, proliferation, invasion, and migration, and increased apoptosis in MDA-MB468 cells. In conclusions, CD44 can serve as a therapeutic target in breast cancer. Moreover, the combination therapy of CD44-specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer.

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Acknowledgements

This work was financially supported by a grant from the National Institute for Medical Research Development (NIMAD), Iran, and Tabriz University of Medical Sciences (Grant No. 58843), Tabriz, Iran.

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Authors and Affiliations

  1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Vahidian, Ali Mohammadi, Shiva Najjary, Behzad Mansoori, Ayoub Aghanejad, Mahdi Abdoli Shadbad, Ahad Mokhtarzadeh & Behzad Baradaran

  2. Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Vahidian

  3. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Vahidian, Jafar Majidi & Zohreh Babaloo

  4. Department of Microbiology and Immunology, Faculty of Medicine, Ardebil University of Medical Sciences, Ardabil, Iran

    Elham Safarzadeh

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  1. Fatemeh Vahidian
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Correspondence to Ahad Mokhtarzadeh or Behzad Baradaran.

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This article does not contain any studies with human participants or animals performed by any of the authors. Ethical code: IR.TBZMED.REC.1396.806.

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Vahidian, F., Safarzadeh, E., Mohammadi, A. et al. siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468). Mol Biol Rep 47, 9541–9551 (2020). https://doi.org/10.1007/s11033-020-05952-z

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  • DOI: https://doi.org/10.1007/s11033-020-05952-z

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