siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expressio
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ORIGINAL ARTICLE
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) Fatemeh Vahidian1,2,3 · Elham Safarzadeh4 · Ali Mohammadi1 · Shiva Najjary1 · Behzad Mansoori1 · Jafar Majidi3 · Zohreh Babaloo3 · Ayoub Aghanejad1 · Mahdi Abdoli Shadbad1 · Ahad Mokhtarzadeh1 · Behzad Baradaran1 Received: 19 June 2020 / Accepted: 28 October 2020 / Published online: 18 November 2020 © Springer Nature B.V. 2020
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 CD44specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer. Keywords Breast cancer · CD44 · siRNA · Doxorubicin
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05952-z) contains supplementary material, which is available to authorized users. * Ahad Mokhtarzadeh [email protected] * Behzad Baradaran [email protected] 1
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2
Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran
3
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4
Department of Microbiology and Immunology, Faculty of Medicine, Ardebil University of Medical Sciences, Ardabil, Iran
Breast cancer is the most prevalent cancer among females worldwide [1]. Since the pathogenesis of breast cancer is heterogeneous, breast cancer patients may show different response rates for a therapeutic approach [2, 3]. Like other solid cancers, metastasis is responsible for 90% of breast cancer mortality in affected patients [4]. In breast cancer, the expression level of CD44 is higher in cancer stem cells (CSCs) than other cancer cells [5]. CD44 is a critical receptor for hyaluronan, matrix metalloproteinases (MMPs), collagens, osteopontin (OPN), and various cytokines like growth factors [6, 7]. The CD44
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