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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)
Molecular Biology Reports ( IF 2.6 ) Pub Date : 2020-11-18 , DOI: 10.1007/s11033-020-05952-z
Fatemeh Vahidian , Elham Safarzadeh , Ali Mohammadi , Shiva Najjary , Behzad Mansoori , Jafar Majidi , Zohreh Babaloo , Ayoub Aghanejad , Mahdi Abdoli Shadbad , Ahad Mokhtarzadeh , Behzad Baradaran

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.



中文翻译:

Pei传递的siRNA介导的CD44沉默增强了阿霉素的化学敏感性,并改变了人乳腺癌细胞系(MDA-MB468)中的miRNA表达

CD44作为一种表面细胞糖蛋白,是细胞与细胞以及细胞与基质相互作用的重要因素。在乳腺癌中,CD44表达水平已被上调,这种上调促进了肿瘤的增殖和血管生成。本研究旨在评估Jet Pei / CD44特异性siRNA /阿霉素在乳腺癌MDA-MB468细胞系中的联合治疗。进行了MTT测定,伤口愈合测试,集落形成测定,DAPI染色和流式细胞术以研究肿瘤细胞的生存力,迁移,克隆形成和凋亡进程。进行定量实时PCR(qRT-PCR)以证明CD44表达水平。最后,测量了CD44沉默对VEGF,CXCR4,MMP9和MiR-142-3p表达的影响。CD44特异性siRNA与阿霉素的结合减少了MDA-MB468细胞的肿瘤转移,增殖,侵袭和迁移,并增加了细胞凋亡。总之,CD44可以作为乳腺癌的治疗靶标。此外,CD44特异性siRNA与阿霉素的联合治疗可能是乳腺癌患者的有前途的治疗方法。

更新日期:2020-11-18
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