Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Mol Biol Rep. 2020 Dec;47(12):9541-9551. doi: 10.1007/s11033-020-05952-z. Epub 2020 Nov 18.
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.
CD44 作为一种细胞表面糖蛋白，是细胞-细胞和细胞-基质相互作用的重要因素。CD44 在乳腺癌中的表达水平显著上调，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/阿霉素联合治疗乳腺癌 MDA-MB468 细胞系。通过 MTT 检测、划痕愈合实验、集落形成实验、DAPI 染色和流式细胞术检测肿瘤细胞活力、迁移、克隆形成和细胞凋亡进展。通过定量实时 PCR（qRT-PCR）检测 CD44 表达水平。最后，测量 CD44 沉默对 VEGF、CXCR4、MMP9 和 MiR-142-3p 表达的影响。CD44 特异性-siRNA 与阿霉素联合应用可降低 MDA-MB468 细胞的肿瘤转移、增殖、侵袭和迁移，并增加细胞凋亡。综上所述，CD44 可作为乳腺癌的治疗靶点。此外，CD44 特异性-siRNA 与阿霉素联合治疗可能是乳腺癌患者的一种有前途的治疗方法。
