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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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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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