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10 April 2019 : Laboratory Research  

Ultrasound-Targeted Microbubble Destruction (UTMD) Combined with Liposome Increases the Effectiveness of Suppressing Proliferation, Migration, Invasion, and Epithelial- Mesenchymal Transition (EMT) via Targeting Metadherin (MTDH) by ShRNA

Juan Xu1A, Yeying Wang1A, Zhizheng Li1BD, Qiannan Wang1F, Xiao Zhou2DF, Wenhai Wu1C*

DOI: 10.12659/MSM.912955

Med Sci Monit 2019; 25:2640-2648

Abstract

BACKGROUND: Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods.

MATERIAL AND METHODS: Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR.

RESULTS: The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line.

CONCLUSIONS: UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.

Keywords: 14-3-3 Proteins, Cell Proliferation, Neoplasm Metastasis, Transfection, Breast Neoplasms, Cell Adhesion Molecules, Cell Movement, Cell Survival, Down-Regulation, Epithelial-mesenchymal transition, Liposomes, Membrane Proteins, Microbubbles, Neoplasm Invasiveness, Prognosis, RNA, Small Interfering, RNA-Binding Proteins, Ultrasonics, Wound Healing

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750